Fluid delivery device

ABSTRACT

An apparatus for accurately infusing fluids into a patient at specific rates over an extended period of time. The apparatus is of a low profile, laminate construction having a stored energy source in the form of a distendable membrane, which in cooperation with the base of the apparatus defines one or more fluid reservoirs each having a fluid inlet and a fluid outlet. The apparatus further includes a novel, conformable ullage made of formable materials. The conformable ullage uniquely conforms to the shape of elastomeric membrane as the membrane returns to its less distend configuration and in so doing can move between a central chamber and a toroidal chamber formed in the cover of the apparatus. This arrangement will satisfy even the most stringent medicament delivery tolerance requirements and will elegantly overcome the limitations of materials selection encountered in devices embodying solely rigid ullage construction. Additionally, the infusion cannula of the apparatus is connected to the base in a novel manner which permits expeditious subdermal delivery to the patient via a cannula which extends generally perpendicularly relative to the base.

BACKGROUND OF THE INVENTION

This is a Divisional of application Ser. No. 08/540,914, filed Oct. 11,1995, now U.S. Pat. No. 5,716,343, which is a Continuation-In-Partapplication of application Ser. No. 08/451,520, filed May 26, 1995 nowU.S. Pat. No. 5,656,032, which is a Continuation-In-Part application ofapplication Ser. No. 08/129,693, filed Sep. 29, 1993 now U.S. Pat. No.5,419,771; which is a Continuation In Part Application of applicationSer. No. 08/069,937, filed May 28, 1993 which has now issued into U.S.Pat. No. 5,336,188; which is a Continuation In Part of application, Ser.No. 08/046,438 filed May 18, 1993 which has now issued into U.S. Pat.No. 5,411,480; which is a Continuation In Part of application Ser. No.07/987,021 filed Dec. 7, 1992 which has now issued into U.S. Pat. No.5,279,558; which is a Continuation In Part application of applicationSer. No. 07/870,269 filed Apr. 17, 1992 which has now issued into U.S.Pat. No. 5,205,820; which is a Continuation In Part of application Ser.No. 07/642,208 filed Jan. 16, 1991, which has now issued to U.S. Pat.No. 5,169,389 which is a Continuation In Part of application Ser. No.07/367,304 filed Jun. 16, 1989 which has now issued to U.S. Pat. No.5,019,047.

FIELD OF THE INVENTION

The present invention relates generally to fluid delivery devices. Moreparticularly, the invention concerns an improved apparatus for infusingmedicinal agents into an ambulatory patient at specific rates overextended periods of time.

DISCUSSION OF THE INVENTION

Many medicinal agents require an intravenous route for administrationthus bypassing the digestive system and precluding degradation by thecatalytic enzymes in the digestive tract and the liver. The use of morepotent medications at elevated concentrations has also increased theneed for accuracy in controlling the delivery of such drugs. Thedelivery device, while not an active pharmacologic agent, may enhancethe activity of the drug by mediating its therapeutic effectiveness.Certain classes of new pharmacologic agents possess a very narrow rangeof therapeutic effectiveness, for instance, too small a dose results inno effect, while too great a dose results in toxic reaction.

In the past, prolonged infusion of fluids has generally beenaccomplished using gravity flow methods, which typically involve the useof intravenous administration sets and the familiar bottle suspendedabove the patient. Such methods are cumbersome, imprecise and requirebed confinement of the patient. Periodic monitoring of the apparatus bythe nurse or doctor is required to detect malfunctions of the infusionapparatus.

Devices from which liquid is expelled from a relatively thick-walledbladder by internal stresses within the distended bladder are well-knownin the prior art. Such bladder, or "balloon" type, devices are describedin U.S. Pat. No. 3,469,578, issued to Bierman and in U.S. Pat. No.4,318,400, issued to Perry. The devices of the aforementioned patentsalso disclose the use of fluid flow restrictors external of the bladderfor regulating the rate of fluid flow from the bladder.

The prior art bladder type infusion devices are not without drawbacks.Generally, because of the very nature of bladder or "balloon"configuration, the devices are unwieldy and are difficult and expensiveto manufacture and use. Further, the devices are somewhat unreliable andtheir fluid discharge rates are frequently imprecise.

The apparatus of the present invention overcomes many of the drawbacksof the prior art by eliminating the bladder and making use of recentlydeveloped elastomeric films, expandable foams and similar materials,which, in cooperation with a base defines a fluid chamber that containsthe fluid which is to be dispensed. The elastomeric film membrane or theexpandable foam member controllably forces fluid within the chamber intofluid flow channels provided in the base.

The elastomeric film materials used in the apparatus of the presentinvention, as well as various alternate constructions of the apparatus,are described in detail in U.S. Pat. No. 5,205,820 issued to the presentinventor. Therefore, U.S. Pat. No. 5,205,820 is hereby incorporated byreference in its entirety as though fully set forth herein. Co-pendingU.S. Ser. No. 08/129,693 filed by the present inventor on Sep. 29, 1993also describes various types of expandable cellular elastomers andelastomeric foams used in making the expandable member of variousphysical embodiments of the invention. This co-pending application isalso hereby incorporated by reference in its entirety as though fullyset forth herein.

The apparatus of the present invention can be used with minimalprofessional assistance in an alternate health care environment, such asthe home. By way of example, devices of the invention can be comfortablyand conveniently removably affixed to the patient's body and can be usedfor the continuous infusion of antibiotics, hormones, steroids, bloodclotting agents, analgesics, and like medicinal agents. Similarly, thedevices can be used for I-V chemotherapy and can accurately deliverfluids to the patient in precisely the correct quantities and atextended microfusion rates over time.

One of the embodiments of the invention described inContinuation-In-Part application Ser. No. 08/129,693 comprises agenerally circular base assembly and a stored energy means provided inthe form of a thin, generally circular shaped, prestressed distendableelastomeric membrane which cooperates with the base assembly to form afluid reservoir. Superimposed over the base assembly is a rigid,distendable membrane engagement means which provides an ullage withinthe reservoir.

The embodiments of the invention described herein comprise improvementsto the devices described in U.S. Pat. No. 5,205,820 and in U.S. Ser. No.08/129,693. More particularly, the inventions described herein aredirected toward providing novel fluid delivery devices which areextremely low profile and are eminently capable of meeting the moststringent of fluid delivery tolerance requirements. In this regard,medical and pharmacological research continues to reveal the importanceof the manner in which a medicinal agent is administered. The deliverydevice, while not an active pharmacological agent, may enhance theactivity of the drug by mediating its therapeutic effectiveness. Forexample, certain classes of pharmacological agents possess a very narrowdosage range of therapeutic effectiveness, in which case too small adose will have no effect, while too great a dose can result in toxicreaction. In other instances, some forms of medication require anextended delivery time to achieve the utmost effectiveness of amedicinal therapeutic regimen.

By way of example, the therapeutic regimens used by insulin-dependentdiabetics provide a good example of the benefits of carefully selecteddelivery means. The therapeutic object for diabetics is to consistentlymaintain blood glucose levels within a normal range. Conventionaltherapy involves injecting insulin by syringe several times a day, oftencoinciding with meals. The dose must be calculated based on glucoselevels present in the blood. If the dosage is off, the bolusadministered may lead to acute levels of either glucose or insulinresulting in complications, including unconsciousness or coma. Overtime, high concentrations of glucose in the blood can also lead to avariety of chronic health problems, such as vision loss, kidney failure,heart disease, nerve damage, and amputations.

A recently completed study sponsored by the National Institutes ofHealth (NIH) investigated the effects of different therapeutic regimenson the health outcomes of insulin dependent diabetics. This studyrevealed some distinct advantages in the adoption of certain therapeuticregimens. Intensive therapy that involved intensive blood glucosemonitoring and more frequent administration of insulin by conventionalmeans, i.e., syringes, throughout the day saw dramatic decreases in theincidence of debilitating complications.

The NIH study also raises the question of practicality and patientadherence to an intensive therapy regimen. A bona fide improvement ininsulin therapy management must focus on the facilitation of patientcomfort and convenience as well as dosage and administration schemes.Basal rate delivery of insulin by means of a convenient and reliabledelivery device over an extended period of time represents one means ofimproving insulin management. Basal rate delivery involves the deliveryof very small volumes of fluid (1-3 mL.) over comparatively long periodsof time (18-24 hours). As will be appreciated from the discussion whichfollows, the apparatus of the present invention is uniquely suited toprovide precise fluid delivery management at a low cost in those caseswhere a variety of precise dosage schemes are of utmost importance.

In those embodiments of the invention described in U.S. Pat. No.5,205,820 issued to the present inventor and incorporated herein byreference, the fluid delivery apparatus components generally included: abase assembly; an elastomeric membrane serving as a stored energy means;fluid flow channels for filling and delivery; flow control means; acover; and an ullage, which comprised a part of the base assembly. Theullage in these devices typically comprises a semi-rigid structurehaving flow channels leading from the top of the structure through thebase to inlet or outlet ports of the device.

In the rigid ullage configuration, the stored energy means of the devicemust be superimposed over the ullage to form the fluid-containingreservoir from which fluids are expelled at a controlled rate by theelastomeric membrane of the stored energy means tending to return to aless distended configuration in a direction toward the ullage. Withthese constructions, the stored energy membrane is typically used athigh extensions over a significantly large portion of thepressure-deformation curve (FIG. 1A).

Elastomeric membrane materials suitable for use as the stored energymeans must possess certain physical characteristics in order to meet theperformance requirements for a fluid delivery apparatus. Moreparticularly, for good performance, the elastomeric membrane materialmust have good memory characteristics under conditions of highextension; good resistance to chemical and radiological degradation; andappropriate gas permeation characteristics depending upon the endapplication to be made of the device.

Once an elastomeric membrane material is chosen that will optimally meetthe desired performance requirements, there still remain certainlimitations to the level of refinement of the delivery tolerances thatcan be achieved using the rigid ullage configuration. These resultprimarily from the inability of the rigid ullage to conform to the shapeof the elastomeric membrane near the end of the delivery period. Thisnonconformity can lead to extended delivery rate tail-off and higherresidual problems when extremely accurate delivery is required. Forexample, when larger volumes of fluid are to be delivered, the tail-offvolume represents a smaller portion of the fluid amount delivered andtherefore exhibits much less effect on the total fluid delivery profile,but in very small dosages, the tail-off volume becomes a larger portionof the total volume. This sometimes places severe physical limits on therange of delivery profiles that may easily be accommodated using therigid ullage configuration.

An acceptable elastomeric membrane material candidate for the rigidullage configuration must also be drug compatible as is typically incontact with any drug containing fluid disposed within the reservoir.Many currently available elastomeric membrane materials, due to theirchemical composition or means of manufacturing, are not drug compatible.This compatibility restriction, combined with strict physicalrequirements, results in further limitation of available selections forthe candidate elastomeric material for use in devices embodying a rigidullage structure.

As will be better appreciated from the discussion which follows, theapparatus of the present invention provides a unique and novelimprovement for a disposable dispenser of simple but highly reliableconstruction that may be adapted to many applications of use. Aparticularly important aspect of the improved apparatus is theincorporation of a conformable ullage made of yieldable materials, theconformable ullage uniquely conforms to the shape of elastomericmembrane as the membrane returns to its less distended configuration.This novel construction will satisfy even the most stringent deliverytolerance requirements and will elegantly overcome the limitations ofmaterials selection encountered in devices embodying the rigid ullageconstruction. Another significant advantage of the novel ullageconstruction is that the ullage can be located either between the baseand the fluid to be delivered, or alternatively, can be located betweenthe elastomeric membrane and the fluid to be delivered. Further, aplurality of subreservoirs can be associated with a single ullagethereby making it possible to incorporate a wide variety of deliveryprofiles within a single device.

Although the infusion devices described in U.S. Pat. No. 5,205,820 andin U.S. Ser. No. 08/129,693 are very low profile devices, the devices ofthe inventions described herein are designed in a manner so that theycan be of even a lower profile thereby making them ideally suited foruse in dispensing medicinal agents such as insulin and the like.

SUMMARY OF THE INVENTION

It is an object of the present invention to provide an apparatus havinga self-contained stored energy membrane for expelling fluids at aprecisely controlled rate which is of a compact, extremely low profile,laminate construction. More particularly, it is an object of theinvention to provide such an apparatus which is of very low profile sothat it can conveniently be used for the precise infusion ofpharmaceutical fluids, such as insulin and the like, into an ambulatorypatient at controlled rates over extended periods of time.

It is another object of the invention to provide an apparatus of theaforementioned character which is small, compact, highly reliable andeasy-to-use by lay persons in a non-hospital environment.

It is another object of the invention to provide an apparatus asdescribed in the preceding paragraphs which, in one form, can be usedfor intravenous infusion of fluids and, in a second form, can be usedfor subdermal infusion of fluids. In this regard, the apparatus includesa novel and unique delivery cannula having a body portion disposedwithin a circuitous channel formed within the base superstructure of theapparatus and a pierceable portion which extends outwardly from the baseof the apparatus. By constructing the cannula in a circuitousconfiguration, substantial structural stability of the cannula relativeto the base is achieved as compared with a straight cannula protrudingfrom the base.

Another object of the invention is to provide an apparatus whichembodies a soft, pliable, conformable mass which defines an ullagewithin the reservoir of the device which will closely conform to theshape of the stored energy membrane thereby effectively avoidingextended flow delivery rate tail-off at the end of the fluid deliveryperiod.

A further object of the invention is to provide a low profile, fluiddelivery device of laminate construction which can meet even the moststringent fluid delivery tolerance requirements.

Another object of the invention is to provide an apparatus of the classdescribed which includes a conformable ullage construction that can beused with a plurality of fluid reservoirs of the same or differentvolume.

Another object of the invention is to provide an apparatus of thecharacter which includes a novel combination filter and rate controlassemblage disposed intermediate the fluid reservoir outlet and theoutlet port of the device.

Another object of the invention is to provide an apparatus of thecharacter described which, due to its unique construction, can bemanufactured inexpensively in large volume by automated machinery.

Other objects of the invention are set forth in U.S. Pat. No. 5,205,820which is incorporated herein and still further objects will become moreapparent from the discussion which follows.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a top plan view of one form of an ultra low profile device ofthe invention partly broken away to show internal construction.

FIG. 2 is a generally perspective view of the ultra low profile infusiondevice shown in FIG. 1.

FIG. 3 is a cross-sectional view taken along lines 3--3 of FIG. 1.

FIG. 4 is a cross-sectional view taken along lines 4--4 of FIG. 1.

FIG. 4A is an enlarged, fragmentary cross-sectional view of area 4A ofFIG. 4.

FIG. 4B is an enlarged, generally perspective view of the cannula andflow control means of the form of the invention shown in FIG. 1.

FIG. 5 is an enlarged, generally perspective view of an alternate formof infusion cannula of the invention.

FIG. 6 is an enlarged, generally perspective view of still anotheralternate form of infusion cannula.

FIG. 7 is a generally perspective top view an alternate form of theultra low profile infusion device of the invention.

FIG. 8 is a view taken along lines 8--8 of FIG. 7.

FIG. 9 is an enlarged, cross-sectional view taken along lines 9--9 ofFIG. 8.

FIG. 10 is a top plan view of the device of FIG. 7 partly broken away toshow internal construction.

FIG. 11 is a cross-sectional view taken along lines 11--11 of FIG. 10.

FIG. 12 is an enlarged, generally perspective view of a portion of thedevice shown in FIG. 7.

FIG. 12A is a generally perspective view illustrating the membranebiaxial stretching step of the method of the invention.

FIG. 12B is a generally perspective view illustrating an alternatemethod of radially stretching the distendable membrane.

FIG. 12C is a fragmentary, cross-sectional view illustrating theconstruction of the hydraulically actuated gripping fingers that gripthe membrane.

FIG. 13 is a generally perspective view of an alternate form of infusioncannula of the invention.

FIG. 14 is an enlarged, generally perspective view of the fluid inletend of the infusion cannula.

FIG. 15 is a greatly enlarged, generally perspective top view of oneform of the fluid flow control assembly of the invention.

FIG. 16 is a greatly enlarged generally perspective, bottom view of theflow control assembly.

FIG. 17 is a generally perspective, exploded view of the flow controlassembly of the invention of FIGS. 15 and 16.

FIG. 18 is a graphical representation of the range of extension of thedistendable membrane in a rigid ullage type of construction.

FIG. 19 is a graphical representation of the range of extension of thedistendable membrane in a conformable ullage type of construction.

FIG. 20 is a cross-sectional view of yet another embodiment of theinvention showing an infusion device embodying a novel conformableullage rather than rigid ullage.

FIG. 20A is a cross-sectional view similar to FIG. 20, but showing theconfiguration of the device after the fluid has been dispensedtherefrom.

FIG. 21 is a cross-sectional view of the base portion of the embodimentof the invention shown in FIG. 20.

FIG. 21A is a cross-sectional view taken along lines 21A--21A of FIG.21.

FIG. 22 is a cross-sectional view of still another embodiment of theinvention showing an infusion device embodying a conformable ullage anda plurality of subreservoirs.

FIG. 22A is a cross-sectional view taken along lines 22A--22A of FIG.22.

FIG. 22B is a cross-sectional view taken along lines 22B--22B of FIG.22.

FIG. 22C is a cross-sectional view similar to FIG. 22, but showing theconfiguration of the device after the fluid has been dispensedtherefrom.

FIG. 22D is a generally perspective view of the infusion cannula of thedevice shown in FIG. 22.

FIG. 22E is a generally graphical representation depicting the characterof the fluid flow from the dual reservoir apparatus shown in FIG. 22.

FIG. 23 is a generally diagrammatic view of yet another form ofconformable ullage construction of the invention showing two fluidfilled subreservoirs.

FIG. 24 is a generally diagrammatic view similar to FIG. 23, but showingone of the subreservoirs having been emptied of fluid.

FIG. 25 is a generally diagrammatic view similar to FIG. 24 but, showingboth of the subreservoirs having been emptied.

FIG. 26 is a generally diagrammatic view of still another form ofconformable ullage construction of the invention showing foursubreservoirs.

FIG. 27 is a top plan view of yet another embodiment of the inventionpartly broken away to show internal construction.

FIG. 28 is a bottom view of the apparatus shown in FIG. 27, again partlybroken away to show internal construction.

FIG. 29 is a cross-sectional view taken along lines 29--29 of FIG. 28.

FIG. 30 is a cross-sectional view taken along lines 30--30 of FIG. 28.

FIG. 30A is a greatly enlarged, cross-sectional view of the areaindicated as 30A in FIG. 30.

FIG. 30B is a generally perspective exploded view of the embodiment ofthe invention shown in FIGS. 27 through 30.

FIG. 31 is an enlarged, cross-sectional view taken along lines 31--31 ofFIG. 27.

FIG. 32 is a greatly enlarged, cross-sectional view taken along lines32--32 of FIG. 27.

FIG. 33 is a top plan view of another form of the invention partlybroken away to show internal construction.

FIG. 33A is a cross-sectional view taken along lines 33A--33A of FIG.33.

FIG. 33B is a generally perspective, exploded view of the apparatusshown in FIG. 33.

FIG. 33C is a cross-sectional view taken along lines 33C--33C of FIG.33.

FIG. 34 is a generally perspective, exploded view of yet anotherembodiment of the low profile device of the invention partly broken awayto show internal construction.

FIG. 34A is a top plan view of the low profile infusion apparatus shownin FIG. 34, partly broken away to show internal construction.

FIG. 35 is a side-elevational view of the apparatus illustrated in FIG.34.

FIG. 36 is an enlarged, cross-sectional view taken along lines 36--36 ofFIG. 35.

FIG. 36A is an enlarged, fragmentary, cross-sectional view taken alonglines 36A--36A of FIG. 35.

FIG. 36B is a cross-sectional view taken along lines 36B--36B of FIG.34A.

FIG. 37 is a greatly enlarged, fragmentary, cross-section view of thearea indicated as 37 in FIG. 36B.

FIG. 37A is a generally perspective, exploded view of theserpentine-shaped capillary tube and flow control means of the form ofthe invention shown in FIGS. 34 through 37.

FIG. 38 is a generally perspective view of yet another form of lowprofile fluid delivery apparatus of the present invention.

FIG. 39 is a top view of the embodiment shown in FIG. 38, partly brokenaway to show internal construction.

FIG. 40 is a cross-sectional view taken along lines 40--40 of FIG. 39.

FIG. 40A is a greatly enlarged, fragmentary, cross-sectional viewillustrating the construction of the filling subassembly of thisembodiment of the invention.

FIG. 41 is a right-side elevational view of the apparatus of FIG. 38.

FIG. 42 is an enlarged, cross-sectional view taken along lines 42--42 ofFIG. 41.

FIG. 42A is a cross-sectional view similar to FIG. 42, but showing thestored energy means having moved into a less distended configuration.

FIG. 42B is an enlarged, generally perspective view of the hollowcannula subassembly of this latest form of the invention.

FIG. 43 is a generally perspective, exploded view of yet anotherembodiment of the fluid delivery apparatus of the invention.

FIG. 44 is an enlarged top plan view of the embodiment shown in FIG. 43partially broken away to show internal construction.

FIG. 45 is an enlarged cross-sectional view taken along lines 45--45 ofFIG. 44.

FIG. 46 is a front view of the apparatus shown in FIG. 44.

FIG. 47 is an enlarged cross-sectional view taken along lines 47--47 ofFIG. 46.

FIG. 47A is a cross-sectional view taken along lines 47A--47A of FIG.44.

FIG. 47B is a greatly enlarged, cross-sectional view of the areaidentified as FIG. 47B in FIG. 47A.

FIG. 47C is a generally perspective, exploded view of the infusioncannula subassembly filter means of this latest form of the invention.

FIG. 48 is a generally perspective, exploded view of the infusioncannula subassembly and filter means of the invention greatly enlargedover the view shown in FIG. 47C and including an exploded view of thefilling subassembly of the apparatus.

FIG. 48A is an enlarged, cross-sectional, assembled view of the fillingsubassembly of the invention.

FIG. 49 is a generally perspective, exploded view of an alternate formof infusion cannula, filter means and filling subassembly of theinvention.

FIG. 49A is a fragmentary, generally perspective view of the enlargeddiameter end portion of the infusion cannula shown in FIG. 49.

FIG. 50 is a greatly enlarged, cross-sectional view taken along lines50--50 of FIG. 49A.

FIG. 50A is a cross-sectional view taken along lines 50A--50A of FIG.50.

FIG. 51 is a generally perspective, exploded view of yet another form ofinfusion cannula subassembly and filter means of the invention.

FIG. 52 is a cross-sectional view of yet another form of infusioncannula subassembly of the invention.

FIG. 53 is a top plan view of still another form of the low profileinfusion apparatus of the invention partly broken away to show internalconstruction.

FIG. 54 is a cross-sectional view taken along lines 54--54 of FIG. 53.

FIG. 55 is a fragmentary, cross-sectional view taken along lines 55--55of FIG. 54.

FIG. 56 is a cross-sectional view taken along lines 56--56 of FIG. 54

FIG. 57 is a cross-sectional view taken along lines 57--57 of FIG. 54.

FIG. 58 is a bottom view of this latest embodiment, partly broken awayto show internal construction.

FIG. 59 is a generally perspective, exploded view of the capillary tubeand flow control means of the form of the invention shown in FIGS. 53through 58.

FIG. 60 is a generally perspective view of the protective sheath portionof the form of the invention shown in FIGS. 53 through 59.

FIG. 61 is a generally perspective, exploded view of still anotherembodiment of the fluid delivery apparatus of the invention.

FIG. 62 is a top plan view of the embodiment shown in FIG. 61 partiallybroken away to show internal construction.

FIG. 63 is a cross-sectional view taken along lines 63--63 of FIG. 62.

FIG. 64 is an enlarged cross-sectional view of the area designated bythe numeral 64 in FIG. 63.

FIG. 65 is an enlarged, cross-sectional view taken along lines 65--65 ofFIG. 62.

FIG. 66 is an enlarged, cross-sectional view taken along lines 66--66 ofFIG. 62.

FIG. 67 is a top plan view of the base portion of still another form ofthe low profile infusion apparatus of the invention partly broken awayto show internal construction.

FIG. 68 is an exploded, cross-sectional view of this latest form of theinvention showing the base portion superimposed over the separationmembrane, the distendable membrane and the cover of the apparatus.

FIG. 69 is a cross-sectional view of the apparatus of FIG. 68 shown inan assembled configuration.

FIG. 70 is an enlarged cross-sectional view taken along lines 70--70 ofFIG. 67.

FIG. 71 is a cross-sectional view of the area designated as 71 in FIG.69.

FIG. 72 is a top plan view of the base portion of yet another form ofthe low profile infusion apparatus of the invention partly broken awayto show internal construction.

FIG. 72A is a generally perspective view of the cannula and septumassembly of this latest form of the invention.

FIG. 73 is an exploded, cross-sectional view of the form of theinvention shown in FIG. 72 illustrating the base portion superimposedover the rate control device, the distendable membrane, and the cover ofthe apparatus.

FIG. 74 is a cross-sectional view of the apparatus of FIG. 73 shown inan assembled configuration.

FIG. 74A is a fragmentary, cross-sectional view similar to FIG. 74, butshowing fluid being expelled from the fluid reservoir of the device.

FIG. 75 is a top plan view of the base portion of still another form ofthe low profile infusion apparatus of the invention partly broken awayto show internal construction.

FIG. 75A is an exploded, cross-sectional view of the form of theinvention shown in FIG. 72 illustrating the base portion superimposedover the rate control device, the distendable membrane, and the cover ofthe apparatus.

FIG. 76 is a cross-sectional view taken along lines 76--76 of FIG. 75.

FIG. 77 is a fragmentary, cross-sectional view of the central portion ofthe device.

FIG. 77A is a fragmentary, cross-sectional view similar to FIG. 77, butshowing fluid being expelled from the fluid reservoir.

FIG. 78 is an enlarged, generally perspective view of one of the fillingsubassemblies of the form of the invention shown in FIGS. 75 through 76.

FIG. 79 is an enlarged, generally perspective view of cannula assemblyof the apparatus of the invention shown in FIGS. 75 and 76.

FIG. 80 is a top plan view of the base portion of still another form ofthe low profile infusion apparatus of the invention partly broken awayto show internal construction.

FIG. 81 is a generally perspective view of the cannula, septum assembly,and fluid outlet assembly of the latest form of the invention.

FIG. 82 is an enlarged, cross-sectional view taken along lines 82--82 ofFIG. 80.

FIG. 83 is an exploded, cross-sectional view of the form of theinvention shown in FIG. 80 illustrating the base portion superimposedover the rate control device, barrier member, the distendable membrane,and the cover of the apparatus.

FIG. 84 is a generally enlarged, fragmentary, cross-sectional view ofthe septum assembly of the invention shown in FIG. 83.

FIG. 85 is a greatly enlarged, fragmentary, cross-sectional view of analternate form of the septum assembly.

FIG. 86 is an enlarged, cross-sectional view of the apparatus of FIG. 83shown in an assembled configuration.

FIG. 87 is a cross-sectional view similar to FIG. 86, but showing fluidbeing expelled from the fluid reservoir of the device.

FIG. 88 is a top plan view of the base portion of yet another form ofthe low profile infusion apparatus of the invention partly broken awayto show internal construction.

FIG. 89 is a generally perspective view of the cannula of this latestform of the invention.

FIG. 90 is an enlarged view taken along lines 90--90 of FIG. 88.

FIG. 91 is an exploded, cross-sectional view of the form of theinvention shown in FIG. 88 illustrating the base portion superimposedover the rate control device, the first barrier membrane, a secondbarrier membrane, the distendable membrane, and the cover of theapparatus.

FIG. 92 is an enlarged, generally perspective, exploded view of thefluid outlet subassembly of this latest form of the invention.

FIG. 93 is an enlarged, cross-sectional taken along lines 93--93 of FIG.88.

FIG. 94 is an enlarged, cross-sectional view similar to FIG. 93, butshowing fluid being expelled from the fluid reservoir of the device.

DESCRIPTION OF THE INVENTION

Referring to the drawings and particularly to FIGS. 1 through 4, oneform of the ultra low profile device of the invention for use inintravenous infusion of medicinal fluid into a patient is there shownand generally designated by the numeral 20. As best seen by referring toFIGS. 3 and 4, the embodiment of the invention there shown comprises athin base 22 having an upper surface 24 including a central portion 24aand peripheral portion 24b circumscribing central portion 24a. Base 22is provided with a lower surface 26 which is engageable with the patientwhen the device is taped or otherwise removably affixed to the patient.Formed within base 22 is a circuitous channel 30 (FIGS. 1 and 2), thepurpose of which will presently be described.

Forming an important aspect of the apparatus of the present invention isstored energy means for forming in conjunction with base 22 a reservoir32 having an outlet 34 (FIG. 1) which is superimposed over channel 30 inthe manner shown in FIGS. 1 and 2. The stored energy means is hereprovided in the form of at least one distendable membrane 37 which issuperimposed over base 22 and is distendable as a result of pressureimparted by fluids introduced into reservoir 32 through a fluid inlet 39(FIG. 3). As member 37 is distended, internal stresses will beestablished within the membrane, which stresses tend to move themembrane toward a less distended configuration and in a direction towardbase 22.

Provided within reservoir 32 is ullage defining means for engagementwith membrane 37 as the membrane tends to return to its less distendedconfiguration. The ullage defining means in the embodiment of theinvention shown in FIGS. 1 through 4 comprises an upstanding,substantially rigid protuberance 40 formed on central portion 24a ofbase 22. Protuberance 40 is preferably integrally formed with base 22.As membrane 37 returns to toward its original configuration, it willmove toward engagement with the upper surfaces of ullage protuberance 40and in so doing will efficiently force fluid contained within reservoir32 uniformly outwardly of the device through fluid outlet 34.

Superimposed over the base assembly, which here comprises base 22,protuberance 40 and distendable membrane 37, is a plastic cover, orenclosure 42. For certain applications, cover 42 may be constructed of aporous material and may include venting means shown here as vent "V"(FIG. 2) for venting gases, if any, contained interiorly of the cover.Additionally, medicament and instructions labels can be affixed to cover42 to identify the medicinal fluid contained within reservoir 32 of thedevice.

Reference should be made to U.S. Pat. No. 5,169,389 for a discussion ofthe device labeling and venting and of the various materials that can beused to construct base 22, distendable membrane 37, and cover 42.

A unique aspect of the infusion device of the present inventioncomprises an infusion means for infusing medicinal fluid from fluidreservoir 32 into the patient. The infusion means here comprises acircuitously shaped hollow cannula 46 having a body portion 46a which isdisposed within circuitous channel 30 formed in base 22 and an outletend 46b here provided in the form of a pierceable portion which extendsoutwardly from base 22 for insertion into the vein of a patient. Forthis purpose, pierceable portion 46b includes a sharp, needle-likeextremity 47 which is configured in generally the same fashion as aconventional intravenous infusion needle.

In the form of the invention shown in FIGS. 1 through 4, pierceableportion 46b of the cannula extends outwardly from base 22 in a directiongenerally parallel to lower surface 26 of base 22. With this uniqueconstruction, the device can be affixed to the patient's body as, forexample, the arms or legs in any convenient manner, with the pierceableneedle portion of the device penetrating the patient's vein. Medicinalfluid contained within reservoir 32 can then be dispensed through thecannula by means of the stored energy provided by membrane 37 which isreleased as the membrane tends to return toward a less distendedconfiguration and into engagement with the ullage defining means orprotuberance 40.

Forming a part of the proximal portion of the device is a protectivesheath 49 for encapsulating and protecting pierceable portion 46b of thecannula. This assembly also includes web means for further assisting insecuring and maintaining the penetrable portion in an appropriateinvasive position to preclude intravascular trauma. Web means is hereprovided as a soft, flexible butterfly assemblage 49a (FIGS. 1 and 2),which is connected to base 22 and provides an appropriate surface areafor taping the device to the patient.

As best seen by referring to FIGS. 3 and 4B, body portion 46a of cannula46 is provided with a fluid inlet 46c which communicates with the outlet34 of reservoir 32 so that fluid can flow from the reservoir into inlet46c through cannula 46 and outwardly thereof through pierceable portion46b.

Filling of reservoir 32 with a selected beneficial agent, or medicinalfluid, is accomplished by filling means which here comprises a septumassembly 52 which is connected to base 22 in the manner shown in FIGS. 1and 2. Septum assembly 52 includes a pierceable septum 54 and a fillconduit 56 which communicates with cannula 46 and fluid inlet 39. Asshown in FIG. 3, inlet 39, in turn, communicates with a fill orifice 58provided in top surface 24 of base 22. With this construction, medicinalfluid can be introduced into reservoir 32 using a conventional syringe.Alternatively, the fill means can comprise a luer fitting or any othersuitable fluid interconnection of a character well known to thoseskilled in the art by which fluid can be controllably introduced intoreservoir 32 to cause distendable membrane 37 to move into its distendedconfiguration as shown in FIGS. 3 and 4. Once again, reference should bemade to U.S. Pat. No. 5,169,389 for a more complete discussion of theconstruction and operation of the reservoir filling means.

Forming another very important aspect of the apparatus of the presentinvention is fluid flow control means which is supported by base 22 at alocation proximate the first end of circuitous channel 30. The fluidflow control means functions to control fluid flowing from reservoir 32into cannula 46 and outwardly through pierceable portion 46b of thecannula. This fluid flow control means here comprises a porous member 51which is received within a cavity 53 formed in base 22. Member 51 can beconstructed of various materials such as a porous polycarbonate materialavailable from Corning Costar Corporation and like suppliers.

Turning now to FIGS. 5 and 6, it is to be observed that the circuitouslyshaped cannula can be constructed in a number of differentconfigurations including those shown in FIGS. 5 and 6. The cannula shownin FIG. 5 and generally designated as 55 has a generally Z-shaped bodyportion, while the cannula shown in FIG. 6 and generally designated bythe numeral 57 comprises a body portion 57a which is vertically offsetfrom the penetrable portion 57b. Depending upon the end use of thedevice and the configuration of base 22, cannulas having configurationssuch as those shown in FIGS. 5 and 6 can be appropriately positionedwithin corresponding circuitously shaped channels formed in base 22.

Referring next to FIGS. 7 through 14, an alternate form of the ultra lowprofile device of the invention is there shown and generally designatedby the numeral 100. As best seen by referring to FIGS. 7, 9, and 11, theembodiment of the invention is similar in some respects to that shown inFIGS. 1 through 7. Accordingly, like numbers are used to identify likecomponents. The apparatus here comprises a thin base 102 (FIG. 9) havingan upper surface 104 including a central portion 104a and peripheralportion 104b circumscribing central portion 104a. Base 102 is providedwith a lower surface 106 to which a padded assembly 107 is connected.Assembly 107 comprises a foam pad 107a to which an adhesive layer 107bis annexed. When the device is used, a very thin peal strip 107c can bestripped away so that the device can be releasably affixed to thepatient. Formed within base 104 is a circuitous channel 110 (FIGS. 11and 12), the purpose of which will presently be described.

In the previously described embodiment, the apparatus shown in FIGS. 7through 14 also includes stored energy means for forming in conjunctionwith base 102 a reservoir 112 having an outlet 114 (FIG. 12) which issuperimposed over channel 110 in the manner shown in FIGS. 11 and 12.The stored energy means is here provided in the form of at least onedistendable membrane 117 which is superimposed over base 102. Membrane117 is distendable as a result of pressure imparted on the membrane byfluids introduced into reservoir 112 through a fluid inlet 119 (FIG.11). As member 117 is distended internal stresses will be established,which stresses tend to move the membrane toward a less distendedconfiguration and in a direction toward base 102.

Provided within reservoir 112 is ullage defining means for engagementwith membrane 117 as the membrane tends to return to its less distendedconfiguration. The ullage defining means in the embodiment of theinvention shown in FIGS. 7 through 12 comprises an upstandingprotuberance 120 formed on central portion 104a of base 102. As membrane117 returns to toward its original configuration, it will move towardengagement with the upper surfaces of ullage protuberance 120 and in sodoing will efficiently force fluid contained within reservoir 112uniformly outwardly of the device through fluid outlet 114.

Superimposed over the base assembly is a plastic cover, or enclosure122. Cover 122 includes a body portion 122a and an outer covering 122b,venting means for venting gases, if any, contained interiorly of thecover. This venting means here comprises a porous vent member 121provided in cover 122 (FIG. 11). As before, medicament and instructionslabels "L" can be affixed to cover 122 to identify the medicinal fluidcontained within reservoir 112 of the device.

Once again, reference should be made to U.S. Pat. No. 5,169,389 for adiscussion of the various materials that can be used to construct base102, distendable membrane 117, and cover 122.

A unique aspect of the infusion device shown in FIGS. 7 through 14comprises an infusion means for infusing medicinal fluid from fluidreservoir 112 into the patient. The infusion means here comprises acircuitously shaped hollow cannula 126 having a body portion 126a whichis disposed within circuitous channel 110 formed in base 102 and anoutlet end 126b here provided in the form of a pierceable portionextending generally perpendicularly downward from base 102 for subdermalinfusion of medicinal fluids into the patient. For this purpose,pierceable portion 126a includes a sharp needle-like portion 127 whichis configured in generally the same fashion as a conventional infusionneedle. Unlike the earlier described embodiment of the invention,pierceable portion 126b of the cannula of the present embodiment extendsoutwardly from base 102 in a direction generally perpendicularly tolower surface 106 of base 102. With this unique construction, the devicecan be affixed to the patient's body, such as the arms or legs, in anyconvenient manner with the pierceable needle portion of the devicepenetrating the skin. Medicinal fluid contained within reservoir 112 canthen be subdermally injected into the patient as membrane 117 tends toreturn toward a less distended configuration and into engagement withthe ullage means or protuberance 120. Forming a part of the proximalportion of the device is a protective sheath 129 for encapsulating andprotecting pierceable portion 126b of the cannula.

As best seen in FIGS. 13 and 14, body portion 126a of cannula 126 isprovided with a fluid inlet 126c which communicates with outlet 114 ofreservoir 112 so that fluid can flow from the reservoir into inlet 126cand then in cannula body 126a via a fluid flow control means mountedwithin a cavity 130 formed in base 102.

The fluid flow control means of this latest form of the inventionfunctions to control fluid flowing from reservoir 112 into cannula 126and then outwardly through pierceable portion 126b of the cannula.Turning to FIGS. 15, 16, and 17, the flow control means of this latestform of the invention can be seen to comprise an assemblage of thegeneral configuration shown in FIGS. 15 and 16 which assemblage isreceivable within a cavity 130 formed in base 102 (FIG. 11). This fluidflow control assemblage, which is generally designated by the numeral131, is of a laminate construction comprising filtering means forfiltering the fluid flowing outwardly of reservoir 112 and rate controlmeans for controlling the rate of fluid flow from reservoir 112 intocannula 126. Referring to FIG. 17, it can be seen that the filter meanshere comprises a filter element 131a while the rate control elementcomprises a disk-like rate control element 131b. Superimposed overfilter element 131a is a porous disk-like seal member 131c. Theassemblage comprising filter element 131a, rate control element 131b,and porous seal 131c is supported by a porous base substrate 131d havinga semi-circular shaped cavity 133 which is adapted to closely receivethe first end portion of cannula 126. Filter element 131a can beconstructed from a wide variety materials. However, a materialcomprising polysulfone sold by Gelman Sciences under the name and styleof SUPOR has proven satisfactory. Rate control element 131b ispreferably constructed from a polycarbonate material having extremelysmall flow apertures ablatively drilled by an excimer laser ablationprocess. Both the orifice size and unit distribution can be closelycontrolled by this process. However, a number of other materials can beused to construct this element. Porous substrate 131d can similarly beconstructed from various materials such as a porous polypropyleneavailable from Gelman Sciences.

Turning to FIGS. 12, 13, and 14, it is to be observed that thecircuitously shaped cannula can be constructed in a number of differentconfigurations. For example, the cannula shown in FIG. 12 has agenerally semi-circular shaped body portion 126a while the cannula 135shown in FIG. 13 has a generally U-shaped body portion 135a. Bothcannula construction as shown in FIGS. 12 and 13 include an inletportion of the character shown in FIG. 14. The generally trough-shapedinlet portion 126c is disposed proximate first end 110a of channel 110and, as shown in FIG. 11, is located directly below flow controlassembly 131 so that fluid flowing through the flow control assemblywill feed directly into cannula 126.

Filling of reservoir 112 with a selected beneficial agent, or medicinalfluid, is accomplished by filling means which here comprises a septumassembly 52 of the character previously described. Septum assembly 52 isconnected to base 102 in the manner shown in FIGS. 10 and 11. Septumassembly 52 includes a pierceably septum 54 and a fill conduit 103 whichcommunicates with cannula 46 and fluid inlet 119, which, in turn,communicates with fill orifice 119a provided in base 102 (FIG. 11). Withthis construction, medicinal fluid can be introduced into reservoir 112using a conventional syringe.

Referring next to FIG. 12A, an apparatus for use in accomplishing themethod of the invention is there illustrated. In accordance with themethod of the invention for constructing the fluid delivery device, base102 is positioned on a table "T" upon which membrane stretching means isaffixed. The membrane stretching means here provided as a stretching, orelongation fixture "F", functions to bilaterally stretch the membrane inthe manner shown in FIG. 12A to controllably prestress the membrane.Stretching fixture "F" comprises four circumferentially spaced membraneholding clamps 137 each having gripping elements 139 for gripping theedges of the isotropic membrane 117. Each of the clamps 137 is affixedto slide block 141 which is slidably movable along a pair of tablemounted tracks 143 by means of a screw assembly 145 which is carried byan end plate 143a provided on each track 143. Each screw assemblycomprises a threaded rod 145b one end of which is connected to a slideblock 141. As the screw assembly is rotated by means of a handle 145a,the slide block, along with its associated clamp 137 will move outwardlyrelative to stationary base 102. A manual vernier 147 provided on eachscrew assembly provides an indication of the extent of movement of theslide block. By controlled outward movement of the slide blocks in themanner shown in FIG. 12A, the isotopic membrane will be controllablystretched and prestressed to the desired extent.

Turning to FIG. 12B, another type of apparatus usable in carrying outthe method of the invention is there illustrated. This apparatus alsoincludes a membrane stretching fixture "SF" which functions tocontrollably bilaterally stretch the elastomeric membrane 117 in themanner illustrated in FIG. 12B. Stretching fixture "SF" includes aplurality of circumferentially spaced hydraulically actuated membranegripping assemblies 149, each having gripping elements for gripping theedges of the isotropic membrane. Each of the gripping assemblies 149 ismounted on a support table "T", which also supports the hydraulicequipment for operating assemblies 149. This type of equipment is of acharacter well known to those skilled in the art. As the grippingassemblies are actuated following a predetermined extension protocol,the gripping elements will move radially outwardly relative to thecenter of membrane 117 causing it to stretch either uniformly ornon-uniformly depending on the end use of the device. It is to beunderstood that for certain end use applications of the apparatus, thestored energy membrane need not be prestressed.

Also forming a part of the apparatus of FIG. 12A is a centrally disposedsonic welding apparatus "SW", which can be used in a manner well knownby those skilled in the art to interconnect cover assembly 122 to base102. Surrounding the sonic welder are vacuum operated article pick-updevices "PU", which can be used to position the cover assembly of thefluid delivery device relative to the membrane during the assemblyoperation. Each of these pick-up devices includes a generally circularshaped gripping member 151 which is rotatable about a support shaft151a.

After the membrane has been appropriately prestressed, the next step inthe method of the invention comprises affixing the prestressed membraneto the peripheral portion 104b of the upper surface of base 102. This isaccomplished by moving cover assembly 122 downwardly relative to base102 in a manner such that prestressed membrane 117 will be securelyclamped between the peripheral portions of cover 122 and the peripheralportion of the base (see FIGS. 9 and 11). As the cover is moved towardbase 102, the central portion of membrane 117 will engage and conform tothe ullage defining means or protuberance 104.

Cover 122 as well as membrane 117 can be interconnected with the base asby sealably bonding them to the base 102 in various ways well known tothose skilled in the art, such as, for example, adhesive or sonicbonding. In the embodiment of the invention shown in FIGS. 9 and 11,peripheral portion 104b of base 102 is provided with a capture groove104c and an adjacent tongue 104d. Body portion 122a of assembly cover122, on the other hand, is provided with a groove 123 and a tongue 123a(FIG. 11) which mate with groove 104c and tongue 104d respectively asthe cover moves into engagement with base 102. Base 102 is furtherprovided with an upstanding membrane cutting means or protuberance 104e(FIG. 11) which functions to cleanly cut membrane 117 upon cover 122being brought into pressural engagement with base 102. With thisconstruction, following cutting of the membrane the cover can besonically welded to the base in the proximity of the upstanding tongueof the base and the mating groove in the cover by techniques wellunderstood by those skilled in the art. After the sonic welding step,the cover and membrane are securely interconnected with the base in amanner to provide a sealed enclosure for the distendable membrane.

Referring to FIGS. 20 and 21, still another form of the ultra lowprofile device of the invention is there shown and generally designatedby the numeral 150. As best seen by referring to FIG. 20, this latestembodiment of the invention is similar in some respects to that shown inFIGS. 7 through 12. Accordingly, like numbers are used to identify likecomponents. The apparatus here comprises a base 152 having an uppersurface 154, including a central portion 154a and peripheral portion154b circumscribing central portion 154a. Base 152 is also provided witha lower surface 156. Formed within base 152 is a circuitous channel 160,which receives the infusion means of the invention.

As in the previously described embodiments, the apparatus shown in FIGS.20 and 21 also includes stored energy means for forming in conjunctionwith base 152 a reservoir 162 having an outlet 164. Outlet 164 issuperimposed over channel 160 in the manner shown in FIG. 20. Filling ofreservoir 162 is accomplished in the same manner as previously describedherein in connection with the embodiment shown in FIGS. 7 through 12using septum assembly 52.

The stored energy means is here provided in the form of at least onedistendable membrane 167 which is superimposed over base 152. As before,an ullage defining means is disposed within reservoir for engagementwith membrane 167 which, after being distended, will tend to return toits less distended configuration. The ullage defining means of thislatest embodiment of the invention is of a totally different and highlynovel character from that previously described. More particularly, theullage defining means here comprises a conformable ullage which uniquelyconforms to the shape of the distendable membrane, as the membrane tendsto return to its less distended configuration in the manner shown inFIG. 20A. The conformable ullage, which is identified in FIGS. 20 and20A by the numeral 170, can be constructed as a deformable mass from anumber of materials such as various types of gels, foams, fluids andsoft elastomers. In some instances the conformable ullage may comprisean integral conforming mass. In other instances, such as when a gel orfluid is used as the ullage medium, an encapsulation barrier membrane isused to encapsulate the ullage medium.

A highly novel aspect of the conformable ullage of the invention residesin the fact that it can be located either between the base and the fluidto be delivered or, alternatively, as shown in FIG. 20, can be locatedbetween the distendable membrane and the fluid to be delivered.Additionally, as will be discussed in the paragraphs which follow, aplurality of subreservoirs can be associated with a single ullagethereby making it possible to provide a wide variety of differentmedicament delivery regimens.

Because the ullage defining means can be located in various locationswithin the reservoir, the central portion of the base is, as shown inFIG. 21, substantially flat. This type of base can, of course, be usedwith an ullage configuration of the character shown in FIG. 20 and canalso be used with a variety of different ullage configurations, thedetails of which will presently be described.

Before discussing the number of conformable ullage configurations thatare possible in constructing the fluid delivery devices of theinvention, a brief discussion will be undertaken of the severaloperational advantages that are inherent in the conformable ullageconstruction. For example, the rigid ullage construction, such as isshown in FIGS. 1 through 14, requires that the stored energy elastomericmembrane be used at high extensions over a significantly large pressurecurve. This condition is illustrated in FIG. 18 wherein inflatingpressure is plotted against height. Further, the elastomeric membranematerials that are suitable for use as the stored energy means mustpossess certain specific physical characteristics in order to meet theperformance requirements for the fluid delivery apparatus. For example,depending on the end use of the device, the elastomeric membranematerial must have good memory characteristics under conditions of highextension, good resistance to chemical and radiological degradation andappropriate gas permeation characteristics.

Once an elastomeric membrane material is chosen that will optimally meetthe desired performance requirements of the fluid delivery device, thereare still limitations to the level of refinement of the deliverytolerances that can be achieved using the rigid ullage configuration.These refinements are due primarily to the inability of the rigid ullageto satisfactorily conform to the shape of the elastomeric membrane nearthe end of the fluid delivery cycle. This nonconformity can lead toextended delivery rate tail off and higher residual problems that areundesirable when extremely accurate delivery is required. For example,when larger volumes of fluid are to be delivered, the tail-off volumerepresents a smaller portion of the fluid amount delivered and,therefore, exhibits much less effect on the total fluid deliveryprofile. However, in very small dosages, the tail-off volume becomes alarger portion of the total volume. This places physical limits on therange of delivery profiles that can acceptably be accommodated by therigid ullage configuration.

The elastomeric membrane material candidates for use in the rigid ullageconstruction must also be drug compatible since the membrane willtypically be in contact with the drug containing fluid that isintroduced into the reservoir. Many currently available elastomericmembrane materials, due to their chemical composition or means ofmanufacturing, are not suitably drug compatible. This compatibilityrestriction, combined with strict physical requirements and materialproperties characteristics, results in further limitation of availableselections for the candidate elastomeric material for use in the rigidullage design.

The apparatus of the invention illustrated in FIG. 20 provides a uniqueand novel improvement over the rigid ullage type devices and, as willbecome apparent from the discussion which follows, can be adapted tomany end use applications. More particularly, this novel embodiment ofthe invention includes the previously identified conformable ullage 170that can be constructed of various materials that will elegantly satisfythe tighter delivery tolerance requirements of the device, while at thesame time effectively overcome the limitations of materials selectionencountered in devices embodying the rigid ullage configuration.

As previously mentioned, the unique characteristics of the conformableullage of this latest form of the invention permits the ullage to beplaced either above or below the fluid reservoir in relation to thebase. For example, when, as indicated in FIG. 19, the conformable ullageis positioned above the medicament reservoir, a much smaller portion ofthe pressure-deformation curve can be used, thus enabling the storedenergy membrane to undergo less deformation during the fluid deliveryprocess. Less deformation of the stored energy membrane, in turn,minimizes the changes in the linearity of the resulting fluid deliveryprofile. Further, because the small portion of the pressure-deformationcurve that is used can be taken from a lower elongation level (FIG. 19),the viscoelastic effect is reduced. The viscoelastic effect reduces thelevel of stored energy in the membrane over time, which translates intolower rates of energy membrane stress relaxation over time. This is amost important performance design factor for devices requiring prolongedshelf life having extended delivery profiles.

Referring once again to FIG. 20, in the construction of the device thereshown, a cover assembly 173 is superimposed over base 152. Coverassembly 173 includes a body portion 173a, an outer covering 173b, andventing means comprising a porous vent member 121 of the characterpreviously described. This latest form of the invention also includes aninfusion means for infusing medicinal fluids from fluid reservoir 162 inthe patient. The infusion means comprises a circuitously shaped hollowcannula 175 of the character previously described having a body portion175a which is disposed within circuitous channel 160 formed in base 152and an outlet end 175b here provided in the form of a pierceable portionextending generally perpendicularly downward from base 152 for subdermalinfusion of medicinal fluids into the patient. For this purpose,pierceable portion 175b includes a sharp, needle-like portion 177.Forming a part of the proximal portion of the device is a protectivesheath 179 for encapsulating and protecting pierceable portion 175b ofthe cannula (FIG. 21).

During the step of filling reservoir 162, which is accomplished in themanner previously described, the fluid being introduced into thereservoir under pressure via septum assembly 52 will cause a pushermember 182, which is affixed proximate its periphery to base 152, toengage conformable ullage 170 urging it outwardly against distendablemembrane 167. As the membrane is thus distended, internal stresses willbe formed in the membrane tending to return it to the less distendedconfiguration shown in FIG. 20A. As this occurs membrane 167 will exertforces on conformable ullage 170 which will controllably move it towardbase 152. However, when ullage 170 engages base 152, in the manner shownin FIG. 20A, it will uniquely conform to the upper surface of the baseas well as the three dimensional shape of distendable membrane 167. Inthis way, the conformable ullage will permit the distendable membrane toprovide a constant fluid expelling pressure on the fluid containedwithin the reservoir throughout the fluid delivery cycle, therebyavoiding undesirable delivery rate tail off at the end of the deliveryperiod. This novel linear performance permits the device to meet eventhe most stringent medicinal fluid delivery requirements.

During the fluid delivery step described in the preceding paragraph,fluid will flow from reservoir 162, through outlet 164, through a flowcontrol means and into the inlet through 175c of cannula 175 (FIG. 21a).The flow control means here comprises a flow control assembly 131 of thecharacter shown in FIGS. 15, 16, and 17 and as previously describedherein.

Distendable membrane along with pusher member 182 are secured to base152 in the manner shown in FIG. 20A. More particularly, the peripheralportion 154b of base 152 is provided with a tongue 152a which mates witha groove 173c provided in cover assembly 173 as the cover assembly movesinto engagement with base 152. Base 152 is also provided with anupstanding, circumferentially extending membrane cutting means orprotuberance 152b (FIG. 11) which functions to cleanly cut membrane 167and pusher 182 upon cover assembly 173 being brought into pressuralengagement with base 152. Protuberance 152b also functions as a sonicenergy director for the sonic weldment of base 152 and cover 173. Withthis construction, following cutting of the membrane and the pushermember, the cover can be sonically welded to the base in the proximityof the upstanding tongue of the base and the mating groove in the coverby techniques well understood by those skilled in the art. After thesonic welding step, the cover, membrane, and pusher member are allsecurely interconnected with the base in a manner to provide a sealedenclosure.

Turning to FIG. 22, still a further form of the ultra low profile deviceof the invention is there illustrated and generally designated by thenumeral 200. This embodiment of the invention is similar in somerespects to that shown in FIGS. 20 and 21 and, therefore, like numbersare used in FIG. 22 to identify like components. This apparatus isunique in that it includes two separate fluid containing reservoirs anda conformable ullage disposed between the reservoirs and the storedenergy means. As before, the apparatus comprises a thin base 202 havingan upper surface 204 including a generally planar central portion 204aand a peripheral portion 204b circumscribing the central portion. Formedwithin base 202 is a circuitous channel 206 that receives a circuitouslyshaped cannula 208.

The apparatus shown in FIG. 22 also includes stored energy means forforming in conjunction with base 202 first and second reservoirs 210 and212. Reservoir 212 has an outlet 214 while reservoir 210 has an outlet216 both of which are superimposed over a circuitous channel 206. Bothreservoirs communicate with cannula 208 via flow control means hereshown as first and second flow control assemblies 218 and 220. Thestored energy means is here provided in the form of at least onedistendable membrane 224 which is superimposed over base 202 and isaffixed therewith in the manner shown in FIG. 22 and as described inconnection with the earlier discussed embodiments.

As was the case with the embodiment of the invention shown in FIGS. 20and 21, pierceable portion 208b of the cannula extends outwardly frombase 202 in a direction generally perpendicularly to lower surface ofthe base. With this construction, medicinal fluids contained withinreservoirs 210 and 212 can then be subdermally injected into the patientas membrane 224 tends to return toward the less distended configurationshown in FIG. 22C and into engagement with the ullage means or aconformable ullage 225 which is of similar construction to conformableullage 170. As shown in FIG. 22E, this arrangement of reservoirs resultsin a two phase flow rate delivery profile. Initially, the injection flowrate results from the medicinal fluid flowing from both reservoirs 210(R1) and 212 (R2). In the latter portion of the flow delivery profile,and after the fluid in reservoir 212 is expanded, only the remainingmedicinal fluid in reservoir 210 contributes to the flow. The greaterflow rate in the first phase is intended to accommodate periods where ahigher dosage rate is required, such as the basal delivery rate forinsulin during the daytime. The second phase with its lower flow rate isthen suitable for the basal rate delivery of insulin during the nightwhen less is required. In this manner, one delivery apparatus may beused for an entire 24 hour period.

As indicated in FIG. 22D, body portion 208a of cannula 208 is providedwith a first fluid inlet 226 which communicates with outlet 216 ofreservoir 210 so that fluid can flow from this reservoir into the flowcontrol assembly 218 and then in cannula 208. In similar fashion,reservoir 212 communicates with a second fluid inlet 228 provided incannula 208 via outlet 214 and flow control assembly 220. Flow controlassemblies 218 and 220 are of identical construction to the assemblageshown in FIGS. 15, 16, and 17 and operate in the same manner to controlfluid flow from the two reservoirs outwardly into cannula 208 shown inFIG. 22. A cover assembly 225 covers base 202 in the manner shown inFIG. 22.

During the filling step, reservoir 212 is first filled by fluidintroduced into a passageway 228 (FIG. 22) via a first septum assembly51 which is provided in base 202 in a spaced apart relationship with asecond septum assembly 52. Fluid under pressure flowing throughpassageway 228 will engage a pusher membrane 230 which is affixed at itsperipheral upper surface 204 of base 202. Following filling of reservoir212, reservoir 210 is next filled using the second septum assembly 52which is in fluid communication with a passageway 229 formed in base202. As fluid under pressure enters reservoir 210 via passageway 229,conformable ullage 225 will be urged outwardly against distendablemembrane 224 causing the membrane to move outwardly against the innersurface 225a of cover assembly 225. As the membrane is thus distended,internal stresses will be formed within the membrane.

Upon opening the outlet or delivery port of the device, the distendedmembrane 224 will exert forces on conformable ullage 225 which willcontrollably move it toward base 202 in the manner shown in FIG. 22C. Asbefore, during the infusion step, the ullage will uniquely conform tothe three dimensional shape of the distendable membrane and fluidcontained within reservoir 210 and 212 will be controllably expelledfrom the device. During the infusion step the, distendable membranefunctions to provide a constant, uniform pressure on the fluid withinthe two reservoirs thereby avoiding any undesirable delivery rate tailoff near the end of the delivery period.

Turning next to FIGS. 23, 24, and 25, yet another conformable ullage,distendable membrane and reservoir only construction is therediagrammatically illustrated. In this instance the conformable ullage300 is disposed between distendable membrane 302 and first and secondspaced apart fluid reservoirs 304 and 306 each having separate fluidinlets and fluid outlets. With this construction the contents of thereservoirs can be delivered sequentially by first opening the outlet ofreservoir 304 and then by opening the outlet of reservoir 306. Onceagain, the stored energy source, or elastomeric membrane 302 will actupon the conformable ullage which, in turn, will act upon the reservoirsto cause the fluid contained therein to be controllably expelled throughthe delivery port of the device. For example, as shown in FIG. 24, whenthe outlet of reservoir 304 is opened, ullage 300 will be urgeddownwardly against a yieldable pusher member 304a which defines theextent of reservoir 304, causing fluid to be expelled from thereservoir. Similarly, when the outlet of reservoir 306 is opened, ullage300 will be urged downwardly against a deformable pusher member 306awhich, along with the base define the extent of reservoir 306, causingthe fluid contained within the reservoir to be controllably expelled(FIG. 25, the arrows "F" indicating outward fluid flow via flow controlmeans).

Further exemplifying the remarkable versatility of the conformableullage construction of the present invention is the arrangementdiagrammatically illustrated in FIG. 26, wherein four separatereservoirs 350, 352, 354, and 356 are acted upon by the conformableullage 358 as it is urged toward base 360 by the stored energy means ordistendable membrane 362. As indicated in FIG. 26, reservoirs 350, 352,and 354 are transversely spaced along the upper surface of the base ofthe device, while reservoir 356 is superimposed over reservoir 354. Eachof these reservoirs is provided with a separate inlet so that differentfluids can be introduced into each reservoir. In like manner, eachreservoir is provided with its own outlet so that the fluids containedwithin the reservoir can be sequentially dispensed as the distendablemembrane acts upon the conformable ullage 358 in the manner previouslydescribed.

It is to be understood that in the case of the constructionsdiagrammatically illustrated in FIGS. 22 through 26, the pressureexerted on the fluid reservoirs of the device can be varied dependingupon the distendable membrane material properties, material thickness,footprints and the extension of the membrane. Altering the conformableullage configuration along with the variations in the number andplacement of fluid reservoirs which are to be acted upon by the ullagemakes it possible to readily match a very large number of drug deliveryprotocols.

Referring to FIGS. 27 through 32, yet another form of the ultra lowprofile device of the invention is there shown and generally designatedby the numeral 370. This latest embodiment of the invention is somewhatsimilar to the embodiment shown in FIGS. 7 through 17, but uniquelyincludes a generally toroidal-shaped, conformable ullage and reservoir(see FIG. 29). More particularly, the device here comprises a base 372,having an upper surface 374 including a central portion 374a and aperipheral portion 374b circumscribing central portion 374a. As bestseen in FIG. 30B, base 372 is provided with a lower surface 376 to whicha patient interconnection means or assembly 378 is connected. Thepatient interconnection means here comprises an apertured planar member379 having an adhesive layer "A" on its upper and lower surfaces. Asshown in FIG. 30 and 30B, a needle cap or sheath 380, which includeshaving a generally circular base 380a, is receivable within circularopening 379a of member 379. Depending from base 380a of the sheath is atear-away needle cover 380b which can be separated from base 380a alonga serration 380c (FIG. 30).

Formed within base 372 is a circuitous channel 384 (FIG. 30B) withinwhich a novel spiral-like hollow cannula or capillary 386 is uniquelymounted in a manner presently to be described.

As in the previously described embodiments, the barrier means or barriermembrane 392 cooperates with the upper surface 374 of base 372 to form areservoir 388 having an inlet 411 and an outlet port 390 (FIG. 32) whichare superimposed over channel 384 in the manner shown in FIGS. 30 and30B. The barrier means is here provided in the form of at least oneyieldable membrane 392 which is superimposed over base 372. A storedenergy means is, in turn, superimposed over the fluid reservoir barriermembrane. The stored energy means is here provided in the form of atleast one distendable elastomeric membrane 406. Membranes 392 and 406are distendable as a result of pressure imparted on the membrane byfluids "F" introduced into reservoir 388 through port 411 (FIG. 32). Asmembrane 406 is distended, internal stresses will be established, whichstresses tend to move the membrane toward a less distended configurationand in a direction toward base 372. As previously mentioned, a uniquefeature of this latest embodiment of the invention resides in the factthat the reservoir is generally toroidal in shape with the outerboundary thereof being defined by a toroidal-shaped chamber 396 formedin a cover member 400.

Provided within the toroidal-shaped chamber 396 is ullage defining meansfor engagement with barrier membrane 392 and distendable membrane 406,which cooperate to encapsulate the ullage defining means. The ullagedefining means in the embodiment of the invention shown in FIGS. 28through 32, uniquely comprises a conformable mass which substantiallyconforms to the shape of the distendable membrane as the membrane isdistended. More particularly, as the distendable membrane returns towardits original, less distended configuration, the conformable ullage andthe barrier membrane will conformably follow its movement towardengagement with the upper surface 374 of base 372 and fluid containedwithin the reservoir will flow uniformly outwardly of the device throughport 390 in the direction of the arrow 402 of FIG. 31.

The stored energy means, while shown in the drawings as one distendablemembrane 406, can comprise a laminate construction made up of aplurality of layers of elastomeric materials. The conformable ullage,which is identified in FIGS. 28 through 32 by the numeral 404, can beconstructed from a number of materials such as various types of gels,foams, fluids and soft elastomers. Here the conformable ullage comprisesa gel which is encapsulated between a barrier membrane 392 anddistendable membrane 406 in the manner best seen in FIG. 29. Materialssuitable for use in constructing the base, the cover and the distendablemembrane are discussed in detail in U.S. Pat. No. 5,205,820.

Referring particularly to FIG. 29, in this latest form of the invention,the infusion means for infusing medicinal fluids from reservoir 388 intothe patient comprises the previously identified circuitously shapedhollow cannula 386. Cannula 386 includes a body portion 386a which ismounted within circuitous channel 384 in a highly novel manner presentlyto be described. Cannula 386 also includes an outlet end 386b, hereprovided in the form of a needle-like segment, which extends generallyperpendicularly downward from surface 376 of base 372 for subdermalinfusion of medicinal fluids into the patient. For this purpose, segment386b is provided with a sharp, pointed extremity 386c (see also FIG.31). As previously discussed, protective sheath 380 surrounds andprotects segment 386b of the cannula (FIG. 29).

Filling reservoir 388 is accomplished in the manner previously describedby introducing fluid into the reservoir under pressure via a septumassembly 410 mounted in base 372 (FIGS. 27 and 32). Using a conventionalsyringe assembly "S", fluid can be introduced into the enlarged diameterportion 386d of cannula 386 via the septum assembly 410. During thisfilling step, barrier membrane 392 is yieldably distended outwardlyagainst the conformable ullage 404 controllably moving it along withdistendable member 406 toward cover 400. As the ullage assembly engagesthe upper wall of channel 396, it will uniquely conform to the channelsurface as well as to the varying shape of barrier membrane 392. Withthis construction, when the fluid is dispensed from the device, theconformable ullage will permit the distendable membrane to provide aconstant fluid expelling pressure on the fluid contained within thereservoir throughout the fluid delivery cycle, thereby avoidingundesirable delivery rate tail off at the end of the delivery period.This novel substantially linear performance permits the device to meeteven the most stringent medicinal fluid delivery requirements.

As best seen in FIG. 32, during the fluid delivery step, fluid will flowfrom reservoir 388, through port 390, through a flow control means andthen into the enlarged diameter portion 386d of cannula 386. The flowcontrol means here comprises a flow control assembly 412 (FIG. 31) of acharacter similar to that shown in FIG. 4A and previously describedherein in connection with the embodiment of FIGS. 1 through 4. Afterflowing through the flow control assembly, the fluid will flow outwardlyof the device via the hollow cannula 386.

Barrier member 392, along with distendable membrane 406 are secured tobase 372 in the manner best seen in FIG. 32. More particularly, theperipheral portion of base 372 is provided with an upstanding, generallycircularly shaped tongue 414 which is received within a groove 416provided in cover 400 as the cover assembly mateably engages base 372.Base 372 is also provided with an upstanding, circumferentiallyextending membrane cutting means or protuberance 418 (FIG. 30A).Protuberance 418 functions to cleanly cut both barrier membrane 392 anddistendable membrane 406 upon the cover assembly being brought intopressural engagement with the base. As before, protuberance 418 alsouniquely functions as a sonic energy director for the sonic weldment ofbase 372 and cover 400. With this construction, following cutting of thedistendable membrane and the barrier membrane, the cover can besonically welded to the base in the proximity of the upstanding tongueof the base and the mating groove in the cover by techniques wellunderstood by those skilled in the art. After the sonic welding step,the cover, the distendable membrane, and the barrier membrane are allinterconnected with the base in a manner to provide a tightly sealedenclosure.

Turning once again to FIGS. 28, 29, and 31, it can be seen that part ofthe body portion of the very small diameter spiral cannula 386 isuniquely supported within channel 384 of base 372 by a cannulaencapsulation means shown here as a standard potting compound 422.Compound 422 rigidly supports the body portion of the cannula withinchannel 384 and dynamically supports the outer extremity 386o of thecannula body so that the spring-like inner portion 386i thereof (FIGS.28 and 30) is free to move three dimensionally within channel 384. Withthis highly novel construction, when the device is connected to thepatient with the needle portion 386b of the cannula penetrating thepatient's body, as, for example, the patient's arm or leg, normalmovement by the patient will permit the cannula to move within a potionof channel 384 while the base remains completely stationary. Withoutthis important feature, normal movements by the patient causing flexingof the muscle and tissue would impart loosening forces to the devicewhich, in time, could cause the adhesive pad "A" provided on the base ofthe device to separate from the patient's skin.

With the cannula enclosure subassembly 380 in position over cannulasegment 386b, the reservoir of the device can be filled with thebeneficial agent to be infused through use of a standard syringeassembly "S" having a needle "N" adapted to penetrate the septum 410a ofthe septum assembly (FIG. 32). Fluid flowing under pressure from thesyringe will enter the enlarged diameter portion 386d of cannula 386 andflow in the direction of the arrow 415 in FIG. 32 inwardly of port 411and toward the reservoir of the device. As the fluid under pressureflows into the reservoir, barrier membrane 392 will be distendedoutwardly against the conformable ullage 404 in a manner to causedistendable membrane 406 to move into engagement with the inner surface396a of the toroidal-shaped channel formed in cover 400.

After the reservoir of the apparatus has been filled with theappropriate beneficial agent, the needle cap or covering 380b can beseparated from the assemblage 380 by breaking it along the serration380c (FIG. 29). This done, the device is interconnected with the patientby penetrating the patient's skin with the point 386c of the infusioncannula 386. As the patient's skin and tissue is penetrated by theinfusion needle, the adhesive pad "A" provided on the lower surface ofmember 379 will cause the base of the device to adhere to the patient'sskin. In some instances, it is desirable to provide a protective peellayer over the adhesive pad until the time the device is to be used. Insuch instances, the protective layer is peeled from the lower surface ofmember 379 immediately prior to use of the device.

As previously mentioned, the highly novel manner in which the very smalldiameter cannula 386 is mounted within channel 384 formed in base 372permits the central portion 386i of the infusion cannula to move threedimensionally relative to the base within the limits of channel 384.This important feature permits the base of the device to remainstationary even though movement of the patient's extremities, whichcause flexing of the muscles, skin, and tissue, tend to impart forces onthe needle portion of the cannula which, but for its ability to freefloat within channel 384, would cause loosening of the adhesive pad.

With the device securely interconnected with the patient, and withsheath 380b removed from base 380, distendable membrane 406 will tend toreturn to its less distended configuration. As the distendable membranemoves toward base 372, the conformable ullage 404 will closely conformto the outer surface of the barrier membrane thereby assuring a completeand substantially linear flow of fluid from the reservoir 388, throughthe cannula 386, and into the patient.

Referring to FIG. 30c, an alternate form of needle cover is thereillustrated. This form of the needle cover is similar to that justdescribed save for the fact that a protective sheath assembly furtherincludes a closure means or cap 425 having an inner bore 425a withinwhich cannula portion 386b is sealably received. The outer surface 425bof cap 425 is telescopically received within a central bore 427 providedin the downwardly protruding stem-like extremity 429 of the sheathassembly in the manner shown in FIG. 30C. It is to be noted that thesheath assembly of this form of the invention also includes a portion431 which is receivable within aperture 379a provided in base portion379. With this construction, cap 425 prevents fluid flow from the hollowcannula until sheath 429 is broken away along serration 300c and cap 425is removed from extremity 386b of the infusion cannula.

Turning to FIGS. 33, 33A, and 33C, still a further form of the ultra lowprofile device of the invention is there illustrated and generallydesignated by the numeral 430. This embodiment of the invention issimilar in many respects to that shown in FIGS. 27 through 32 and,therefore, like numbers are used in these figures to identify likecomponents. This apparatus is unique in that the microbore tubing usedto form the body portion of the hollow cannula functions not only as afluid delivery means, but also as a flow rate control means forcontrolling the rate of fluid flow from the device. Additionally, theinner body portion of the cannula is coiled in a unique manner toenhance the ability of the cannula body to move relative to the base ofthe device.

The apparatus of this latest form of the invention includes a base 432which cooperates with a barrier membrane 392, a conformable ullage 404,a distendable membrane 406 and a cover 433 to form a generallytoroidal-shaped reservoir 388, having an inlet 434 and an outlet 436both of which communicate with a delivery cannula 438. As before, aportion of cannula 438 is receivable within a circuitous channel 440formed in base 432. Cannula 438 has an outer segment 438o, an innercoiled portion 438i, and an enlarged diameter end portion 438a. Filtermeans, here provided as a porous filter 442 with fluid impermeablelayment 442a (FIG. 33C), is disposed between the outlet of reservoir 388and an inlet 443 formed in enlarged diameter portion 438a of cannula438. Also formed in the enlarged diameter portion 438a of the cannula isan outlet port 445 which communicates with inlet 434 of reservoir 388.Fluid impermeable layer 442a serves to interrupt the flow and direct itto inlet 445. Outlet port 445 also communicates with a fluid passageway448 formed in enlarged diameter portion 438a, which passageway is sealedat its outboard end by a septum assembly 410 of the character previouslydescribed. Fluid introduced into the device via septum assembly 410 willflow through passageway 448 and then into reservoir 388 via inlet 434.As the fluid enters the reservoir, it will distend the distendablemembrane and moves the conformable ullage in the manner previouslydiscussed.

Turning particularly to FIGS. 33A and 33B, it is to be noted that theouter portion 438o of the cannula is secured in place within channel 440by a suitable encapsulation means, such as the previously describedpotting compound 422. With this construction, the coiled inner portion438i of the cannula is free to move within the portion of channel 440designated as 440a in FIG. 33A. With this unique arrangement, normalmovement by the patient will permit the cannula to move threedimensionally within channel 440a while the base remains completelystationary. Without this important feature, each movement by the patientthat causes flexing of the skin, muscles and tissue could impartundesirable loosening forces to the adhesive pad which, in turn, couldcause the base of the device to become separated from the patient.

Once the device has been removably interconnected with the patient,infusion of the beneficial agent contained within reservoir 388 viacannula 438 is accomplished in the manner previously described. However,in this latest embodiment of the invention, the rate of fluid flow fromthe device is closely controlled by controlling the size of themicrobore portion 438o of the cannula which communicates with passageway448. The diameter of the bore of the microbore tubing used to constructcannula portion 438o can range from between about 0.0002 and about 0.005inches so that the beneficial agent can be controllably disposed overrelatively long periods of time up to 24 hours or longer.

Referring to FIGS. 34 through 37A, still another form of the ultra lowprofile device of the invention is there shown and generally designatedby the numeral 460. As best seen by referring to FIGS. 34 and 34A, thislatest embodiment of the invention is similar in some respects to thatshown in FIGS. 27 through 32. Accordingly, like numbers are used todescribe like components. This embodiment of the invention is unique inthat it includes dual reservoirs which communicate with a novel,serpentine-shaped hollow cannula (FIG. 37A), the character of which willpresently be described.

As best seen in FIGS. 36 and 36a, the apparatus here comprises a base462 having an upper surface 464, including a central portion 464a and aperipheral portion 464b circumscribing central portion 464a. Base 462 isalso provided with a lower surface 466. Formed within base 462 is acircuitous channel 470 (FIG. 34A), which receives a portion of theinfusion means, or serpentine-shaped hollow cannula 472, of theinvention.

The apparatus shown in FIGS. 34 through 37A also includes stored energymeans for forming, in conjunction with the base 462, a pair ofreservoirs 474 and 476 having outlets 478 and 480 respectively. As bestseen in FIG. 34A, outlet 478 is in communication with a first inlet port482 provided in cannula 472, while outlet 480 is in communication with asecond inlet port 484 provided in cannula 472 (FIGS. 34A and 37A).Filling of outer reservoir 474 is accomplished via a first septumassembly 486 which fills through a reservoir inlet 474a and a filterF-1, while filling of central reservoir 476 is accomplished via a secondseptum assembly 488 which fills through a reservoir inlet 476a and afilter F-2 (FIG. 34A) Filters F-1 and F-2 comprise a part of the fillermeans of the invention. Both septum assemblies include a pierceableseptum 486a and are used in the same manner as previously described.

As before, the stored energy means is provided in the form of at leastone distendable membrane 496 which is superimposed over base 462. Anullage defining means is disposed within each reservoir for engagementwith membrane 496 which, after being distended, will tend to return toits less distended configuration. Once again, the ullage defining meansof this latest embodiment of the invention comprises a conformableullage of the general character previously described which uniquelyconforms to the shape of the distendable membrane as the membrane tendsto return to its less distended configuration. The first conformableullage, which is disposed within outer reservoir 474, is identified inFIGS. 36 and 36A by the numeral 492. The second conformable ullage,which is disposed within central reservoir 476, is designated by thenumeral 494. Ullages 492 and 494 each comprise a deformable massconstructed from materials such as gels, foams, fluids and softelastomers. Where, as is here the case, the conformable ullage comprisesa gel, an encapsulation barrier membrane 490 is used to encapsulate theullage medium and separate it from the fluid reservoir. Once again, theconformable ullage is located between the barrier membrane and cover500. More particularly, ullage 492 is located between membrane 490 andan oval shaped channel 502 formed in cover 500, while ullage 494 islocated between membrane 490 and a generally domed-shaped cavity 504formed in cover 500 (FIG. 36B).

Turning particularly to FIG. 37A the serpentine-shaped cannula 472 ofthe device includes a body portion 472a constructed from a length ofmicrobore tubing, an enlarged diameter portion 472b and a needle-likeoutboard extremity 472c. Receivable within inlets 482 and 484 formed inportion 472b are filter means for filtering fluids flowing from the dualreservoirs. These filter means are here provided as porous filtermembers 507 and 509 which can be constructed from various materials suchas polysulfone.

As indicated in FIG. 37, the peripheral portion of the cover 500 isprovided with a capture groove 510 and an adjacent tongue 512.Similarly, base 462 is provided with tongue 514 which mates with groove510 as the cover moves into engagement with base 462. Base 462 isfurther provided with an upstanding membrane cutting means, orprotuberance 516 which functions to cleanly cut the stored energy meansand the barrier membrane 490 upon cover 500 being brought into pressuralengagement with base 462. With this construction, following cutting ofthe membrane the cover can be sonically welded to the base in the mannerpreviously described.

When the cover and base are sealably joined together extremity 472c ofthe infusion cannula extends from the assemblage in the manner shown inFIG. 36B and is covered by a protective cover means or cap assembly 520.Cap assembly 520 comprises an elongated needle cover 520a having acentral bore which closely receives portion 472c of cannula 472 in themanner shown in FIG. 36B. Cap 520a has an outside diameter closelycorresponding to the inside diameter of a sheath 522 which is joinedwith a base extension 462e by means of a serrated portion 462f whichenables sheath portion 522 to be broken away from the base assembly, andalong with cap 520a slidably removed from portion 472c of the cannula.

In using the apparatus of this latest form of the invention, reservoir474 can be filled via septum assembly 486 using a conventional fluidcontaining syringe assembly having a needle "N" adapted to penetrateseptum 486a of septum assembly 486. Similarly, central reservoir 476 canbe filled via septum assembly 488 using a second syringe assemblycontaining a second fluid which is the same or different from the firstfluid used to fill chamber 474. With the chambers thus filled, theprotective covering means which covers 472c of the cannula can be brokenaway and removed and the needle end portion 472c of the device insertedinto the vein of the patient. As before, the base of the device isprovided with a suitable adhesive to enable the device to be removablyaffixed to the patient's body such as to the arm or leg of the patient.Further, the device includes a butterfly assemblage 523 which isintegrally formed with base 462. Assemblage 523 provides appropriatesurface area for tape used to secure the infusion cannula in place.

Once the device is interconnected with the patient, it will beappreciated that the fluids contained within first chamber 474 andcentral chamber 476 will be urged to flow through the cannula as thestored energy means, or distendable membrane 496 tends to return to itsless distended configuration. As before, the conformable ullagescontained within the reservoirs will closely conform to the changingshape of the stored energy means as the stored energy means moves towardsurface 464a and 464b of base 462. However, because the fluid outlet 478of the outer chamber of the device communicates with the enlargeddiameter portion of the cannula at a location further removed fromextremity 472a, fluid flowing from the outer reservoir will flow towardthe patient at a slower rate than will fluid flowing from the centralreservoir via outlet 480. Since the fluid flowing through outlet 480 hasa shorter distance to travel through the cannula than the fluid flowingfrom the outer chamber, the rate of flow of this fluid will be greaterthan the rate of flow of the first fluid contained within the outerchamber. The microbore tubing portion of the cannula assembly 472 thuslyfunctions both as a fluid conduit and as a rate control means forvariably controlling the rate of fluid flowing from the outer andcentral reservoirs of the device.

Referring to FIGS. 38 through 42B, yet another form of the ultra lowprofile device of the invention is there shown and generally designatedby the numeral 525. This latest embodiment of the invention is quitesimilar to the embodiment shown in FIGS. 28 through 32 in that it alsoincludes a generally toroidal-shaped, conformable ullage and reservoir(see FIG. 38). Because of the similarity of this latest form of theinvention to that shown in FIGS. 28 through 32, like numerals will beused to identify like components.

As best seen in FIGS. 38, 39, and 40, the device here comprises a base527, having an upper surface 530 including a central portion 530a and aperipheral portion 530b circumscribing central portion 530a. As before,base 527 is provided with a lower surface to which a patientinterconnection means or member 532 is connected. Member 532 functionsto releasably interconnect the device to the patient by means of anadhesive layer "A". Also connected to base 527 is a protective covermeans including a needle cap or sheath subassembly 534 of a constructionsimilar to that shown in FIG. 30C. Subassembly 534 includes a protectivesheath 536 within which a closure means or cap 538 is telescopicallyreceived. Cap 538 has an inner bore within which penetrable cannulaportion 540c is sealably received. The upper portion of sheath 536 isprovided with a serration 537 so that the sheath, along with cap 538,can be separated from the cannula at time of use.

Unlike the apparatus shown in FIGS. 28 through 32, the hollow cannula orcapillary 540 of this embodiment of the invention is insert moldedwithin base 527 in the manner shown in FIG. 40. However, as in thepreviously described embodiments, barrier membrane 546 cooperates withthe upper surface of base 527 to form a reservoir 548 having aninlet/outlet port 550 (FIG. 40) which is superimposed over enlargeddiameter portion 540b of cannula 540 in the manner shown in FIG. 40. Thebarrier membrane 546, functions in the same manner to accomplish thesame result as previously described herein. As previously mentioned, thereservoir is generally toroidal in shape with the outer boundary thereofbeing defined by a toroidal-shaped channel 552 formed in a cover member525 (FIG. 42A).

Provided within the toroidal-shaped reservoir is ullage defining meansfor engagement with membrane 546 as the membrane moves into itsdistended configuration. The ullage defining means in the presentembodiment, shown here as 554, also operates in the same manner toaccomplish the same result as previously described.

In this latest form of the invention, the infusion means for infusingmedicinal fluids from reservoir 548 into the patient comprises thepreviously identified circuitously shaped hollow cannula 540. Cannula540 includes a body portion 540a which is molded in base 527 in a mannerwell known by those skilled in the art. Cannula 540 also includes anoutlet end, here provided in the form of the needle-like segment 540c,which extends generally perpendicularly downward from base 527 forsubdermal infusion of medicinal fluids into the patient. As before, aprotective sheath assembly 534 surrounds and protects segment 540c ofthe cannula (FIG. 40).

Filling reservoir 548 is accomplished in the manner previously describedby introducing fluid into the reservoir under pressure via a septumassembly 410 mounted in base 527 (FIGS. 40 and 40a). Using aconventional syringe assembly "S", fluid can be introduced into theenlarged diameter portion 540b of cannula 540 via the septum assembly410. During this filling step, barrier membrane 546 is distendedoutwardly against the conformable ullage 554 controllably moving it,along with a distendable membrane 557, toward cover 525. As the ullageassembly engages the upper wall of channel 552, it will uniquely conformto the channel surface as well as the varying shape of distendablemembrane 557. With this construction, when the fluid is dispensed fromthe device, the conformable ullage will permit the distendable membraneto provide a constant fluid expelling pressure on the fluid containedwithin the reservoir throughout the fluid delivery cycle, therebyavoiding undesirable delivery rate tail off at the end of the deliveryperiod.

As best seen in FIG. 40, during the fluid delivery step, fluid will flowfrom reservoir 548, through port 550 through a flow control means shownhere as flow control assembly 412 then into the enlarged diameterportion 540b of cannula 540. Flow control assembly 412 is identical tothat shown in FIG. 30B and functions as described herein.

Distendable member 557, along with barrier membrane 546, is secured tobase 527 in the manner previously described as is cover member 525. Asbefore, protuberance 418 also uniquely functions as a sonic energydirector for the sonic weldment of base 527 and cover 525.

The device of this latest form of the invention is used in a mannersimilar to the apparatus shown in FIGS. 27 through 32 and, therefore,the details of operation of the device will not here be discussed.

Referring to FIGS. 43 through 48A, another form of the ultra low profiledevice of the invention is there shown and generally designated by thenumeral 560. As best seen by referring to FIGS. 43, 44 and 45, thisembodiment of the invention is similar in some respects to that shown inFIGS. 34 through 37A save that the reservoir configuration is differentas is the filling means.

As best seen in FIGS. 43 and 45, the apparatus here comprises a base 562having an upper surface 564, including a central portion 564a and aperipheral portion 564b circumscribing central portion 564a. Base 562 isalso provided with a lower surface 566. Formed within base 562 is acircuitous channel 570 (FIG. 44), which receives a portion of theinfusion means, or serpentine-shaped hollow cannula 572, of theinvention.

As before, this latest form of the invention includes a stored energymeans for forming, in conjunction with the base 562, a generallytoroidal shaped reservoir 576 having an outlet 578. As best seen in FIG.45, outlet 578 is in communication with an inlet port 582 provided incannula 572. Filling of reservoir 576 is accomplished in the mannerpreviously described via a septum assembly 586, which includes apierceable septum 586a that is pierceable by a syringe needle "N" (FIG.45).

As before, the stored energy means comprises at least one distendablemembrane 594 which is superimposed over base 562. An ullage definingmeans is disposed within reservoir 576 for engagement with membrane 594which, after being distended, will tend to return to its less distendedconfiguration. Once again, the ullage defining means of this latestembodiment of the invention comprises a conformable ullage 592 of thegeneral character previously described which uniquely conforms to theshape of the distendable membrane as the membrane tends to return to itsless distended configuration. Ullage 592 is of the general characterpreviously described and includes an encapsulation barrier membrane 590which functions to encapsulate the ullage medium.

Turning particularly to FIGS. 44 and 47C the serpentine-shaped cannula572 of the device includes a body portion 572a constructed from a lengthof microbore tubing, an enlarged diameter portion 572b and a needle-likeoutboard extremity 572c. Receivable within an inlet 572d formed inportion 572b is filter means for filtering fluids flowing from reservoir576. This filter means is here provided as a porous filter member 595which can be constructed from various materials such as polysulfone.

A cover 597 is receivable over base 562 and includes a capture groove600 and an adjacent tongue 602 (FIG. 47B). Similarly, base 562 isprovided with tongue 604 which mates with groove 600 as the cover movesinto engagement with base 562. As before, base 562 is also provided withan upstanding membrane cutting means, or protuberance 606 whichfunctions to cleanly cut the stored energy means and the barriermembrane upon the cover being brought into pressural engagement withbase. With this construction, following cutting of the membrane, thecover can be sonically welded to the base in the manner previouslydescribed.

When the cover and base are sealably joined together extremity 572c ofthe infusion cannula extends from the assemblage in the manner shown inFIGS. 44 and 46 and is covered by a protective cover means or capassembly 520 of the character previously described herein. As before,cap assembly 520 includes a sheath 522 which is joined with a baseextension 562e by means of a serrated portion 562f which enables sheathportion 522 to be broken away from the base assembly, and along with theclosure cap, slidably removed from portion 572c of the cannula.

In using the apparatus of this latest form of the invention, reservoir576 can be filled via septum assembly 586 using a conventional fluidcontaining syringe assembly having a needle "N" adapted to penetrateseptum 586a of septum assembly 586. With the reservoir thus filled, theprotective covering means which covers the end of the cannula can bebroken away and removed and the needle end portion 572c of the deviceinserted into the vein of the patient. As before, the base of the deviceis provided with a suitable adhesive to enable the device to beremovably affixed to the patient's body such as to the arm or leg of thepatient. Further, the device includes a butterfly assemblage 523 whichis integrally formed with base 562 and provides an appropriate surfacearea for tape used to secure the infusion cannula in place.

Once the device is interconnected with the patient, it will beappreciated that the fluids contained within reservoir 576 will be urgedto flow through the cannula as the stored energy means, or distendablemembrane 594 tends to return to its less distended configuration. Asbefore, the conformable ullages contained within the reservoirs willclosely conform to the changing shape of the stored energy means as thestored energy means moves toward the upper surface of the base. Duringthe infusion step, the microbore tubing portion of the cannula assemblyfunctions both as a fluid conduit and as a rate control means forvariably controlling the rate of fluid flowing from the reservoir of thedevice.

Referring to FIGS. 48 through 52, various forms of hollow cannulaconstructions usable with ultra low profile devices of the generalnature described in the preceding paragraphs are there shown. Turningfirst to the hollow cannula construction shown in FIGS. 48 and 48A, itis to be observed that this cannula construction is similar in manyrespects to that shown in FIG. 47C. However, in this construction, theenlarged diameter portion 615b of the hollow cannula 615 is providedwith a fluid outlet port 617 which is adapted to communicate with areservoir inlet of a reservoir defined by an elastomeric membranesuperimposed over a base having an upper surface. More particularly, inthe construction of the embodiment of the invention shown in FIGS. 44through 47C, the reservoir of the device is filled by fluids flowingoutwardly of the enlarged diameter portion 572b via outlet 572d and flowcontrol member 595. In the cannula construction shown in FIG. 48, fluidflows directly to the reservoir through outlet 617 and flow of the fluidis not impeded by the flow control device 595.

As was the case in the earlier described hollow cannula construction,the hollow cannula shown in FIGS. 48 and 48A comprises a needle-likeoutboard extremity 615c and a central portion 615a. At least a portionof the central section 615a of the cannula 615 is formed from a lengthof microbore tubing 619 having a very small diameter microbore fluidflow path 621. By adjusting the size of the microbore fluid passageway621, it is apparent that the rate of fluid flow through the cannula canbe closely controlled.

As was the case with the earlier constructions, enlarged diameterportion 615b of the hollow cannula includes a swagged end portion 623which receives the pierceable septum 586a in the manner shown in FIG.48A.

With the cannula construction shown in FIGS. 48 and 48A, filling of thereservoir can be accomplished very quickly through the use of aconventional syringe having a needle adapted to pierce septum 586a sothat fluid can flow into enlarged diameter portion 615b. The fluidflowing into the enlarged diameter portion can then freely flow into thereservoir via outlet 617 without impedance from the small diametertubing which makes up the body of the hollow cannula and withoutimpedance from the flow control device or filter media 595 with fluidimpermeable layer 595a. Fluid is expelled from the reservoir by thestored energy means in the same manner as previously described herein.During the infusion process, the fluid flows from the fluid reservoir asa result of the urging of the stored energy means, through filter media595, and into the body portion 615a of the cannula. By regulating thediameter of the microbore 621, the amount of fluid flowing from thedevice as a function of time can be closely regulated.

Turning next to FIGS. 49 through 50A, an alternate form of hollowcannula construction is there illustrated. This type of cannulaconstruction is similar in many respects to that shown in FIG. 30B. Thiscannula construction, generally designated by the numeral 625, alsoincludes a central body portion 625a constructed of a microbore tubing,an enlarged diameter end portion 625b, and a needle-like extremity 625cwhich can be used for subdermal infusion of fluids into a patient. As inthe construction shown in FIG. 30B, end portion 625c extends outwardlyfrom the base of the device generally at right angles to the base sothat it can penetrate the skin and tissue of the patient as the base ismoved into proximity with the patient's body.

Like the cannula construction shown in FIG. 48, the enlarged diameterportion 625b of this latest form of hollow cannula also includes anoutlet port 627 which is adapted to communicate with a fluid reservoirdefined by an elastomeric membrane overlaying a base member.

As best seen by referring to FIGS. 50 and 50A, the flow control means,or filter member 630 of this form of the invention, is of a slightlydifferent construction than that previously described and is closelyreceived within a specially configured opening 632 provided in enlargeddiameter portion 625b. More particularly, as shown in FIG. 50, flowcontrol means, or member 630 includes a lower portion 630a which, wheninserted into opening 632, engages the lower wall of the enlargeddiameter portion 625b so as to impede fluid flow in a direction towardcapillary tube portion 625a. As illustrated in FIG. 50A, due to theresistance of fluid flow through member 630, fluid introduced into thedevice via septum assembly 586 will tend to flow outwardly of the hollowcannula through port 627 and into the fluid reservoir of the device.However, as indicated by the arrow 634, in FIG. 50A, fluid flowingoutwardly of the reservoir will flow through the flow control means ormember 630 in the manner illustrated and toward capillary tube portion625a of the hollow cannula.

It is also to be observed by referring to FIG. 49 that the outboardextremity 625c of the hollow cannula includes an enlarged diameter fluidflow passageway 636 which extends substantially the entire length of theperpendicularly extending portion 625c of the hollow cannula. Thisenlarged diameter fluid passageway permits a more rapid fluid flowthrough the extremity than does the capillary bore portion of thecentral body of the hollow cannula.

Turning to FIGS. 51 and 52, yet another form of hollow cannula of theinvention is there illustrated. This hollow cannula is similar in somerespects to that shown in FIG. 49, but includes a plurality of innerspirals which terminate in a needle-like, tissue-penetrating extremityalso having an enlarged diameter fluid passageway 640. Moreparticularly, this hollow cannula construction includes a central bodyportion 642 which spirals inwardly from the swagged end portion 644 ofan enlarged diameter portion 646 of the hollow cannula and terminates atthe generally perpendicularly extending needle-like extremity 648. Onceagain, flared portion 646a is provided with a cavity 650 which closelyreceives a flow control means or member 652.

FIG. 52 is a foreshortened, side-elevational, cross-sectional view ofthe cannula construction shown in FIG. 51, but illustrated in anuncoiled linear configuration. As indicated in FIG. 52, the centralportion of the cannula is provided in the form of a microbore tubinghaving a small diameter microbore fluid passageway 655 whichcommunicates with enlarged diameter fluid passageway 640 provided inextremity 648. As was the case in the earlier described hollow cannulaconstructions, enlarged diameter portion 646 is provided with a fluidoutlet 657 which communicates with the fluid reservoir of the devicewithin which the cannula is mounted. Like the earlier described forms ofthe invention, enlarged diameter portion 646a includes a flared end 646awhich is adapted to receive a septum assembly of the characterpreviously described.

Referring to FIGS. 53 through 60, still another form of the ultra lowprofile device of the invention is there shown and generally designatedby the numeral 660. This latest embodiment of the invention is similarin some respects to the embodiment shown in FIGS. 34 through 37A.However, this embodiment is unique in that while it comprises a singlefluid reservoir 664 disposed within a central chamber 665 it alsoincludes dual ullages which are in communication. More particularly, thedevice includes a central conformable ullage 662, which is in a superiorposition to a central fluid reservoir 664 and a toroidal-shaped,conformable ullage 666. In a manner presently to be described, thisconstruction permits the use of elevated pressures within chamber 665without having to increase the overall height of the device.

As best seen in FIGS. 54 and 55, the apparatus here comprises a base 668having an upper surface 670, including a central portion 670a and aperipheral portion 670b circumscribing central portion 670a. Base 668 isalso provided with a lower surface 672. Formed within base 668 is acircuitous channel 674 (FIG. 53), which receives a portion of theinfusion means, or serpentine-shaped hollow cannula 678, of theinvention (FIG. 59).

The apparatus shown in FIGS. 53 through 60 also includes a barrier meansfor forming, in conjunction with the central portion 670a of the base,reservoir 664 which has an inlet port 680 and an outlet port 682. Asbest seen in FIG. 55, inlet port 680 is in communication with an outletport 684 provided in an enlarged diameter portion 686 of cannula 678.Filling of fluid reservoir 664 is accomplished via a septum assembly 586of the character previously described. As before, a flow control meansor filter media 688 with fluid impermeable layer 688a impedes fluid flowtoward the micro bore portion of the cannula and causes the fluidflowing into the enlarged diameter portion of the cannula via septumassembly 586 to flow through port 684 and toward reservoir 664.

A stored energy means is provided in the form of at least onedistendable membrane 695 which is superimposed over central portion 670aand peripheral parts 670b of the base. The central ullage 662 of theullage defining means is disposed within chamber 665 for engagement withmembrane 695 which, after being distended, will tend to return to itsless distended configuration. As previously mentioned, the ullagedefining means of this latest embodiment of the invention uniquelycomprises not only the central conformable ullage 662, but also theouter toroidal shaped, conformable ullage 666 both of which vary inshape as the distendable membrane distends and, then, during theinfusion step, tends to return to its less distended configuration. Asbest seen in FIGS. 53 and 56, the central conformable ullage 662communicates with the outer toroidal ullage 666 via a plurality ofpassageways 694 which interconnect central chamber 665 with atoroidal-shaped chamber 696 which contains ullage 666. Ullages 662 and666 here each comprise a flowable mass constructed from a gel material.Where, as is here the case, the conformable ullage comprises a flowablegel, an encapsulation barrier member 690 is used to cooperate inencapsulating the ullage medium. As best seen in FIG. 54, barrier member690 comprises a single yieldably deformable membrane which overlays thecentral portion of the base and functions to define the fluid reservoirto be filled with the fluid to be delivered. On the other hand, thedistendable barrier membrane 695 overlays the ullages and in its fullyextended configuration closely conforms to the inner surface 665a ofgenerally domed-shaped chamber 665 formed in cover 700 and to the innersurface 698 of toroidal chamber 696.

Turning particularly to FIGS. 53 and 59, the serpentine-shaped cannula678 of the device includes a body portion 678a which is constructed froma length of microbore tubing, the previously identified enlargeddiameter portion 686, and a needle-like outboard extremity 678b.Receivable within an opening 702 formed in portion 686 is the previouslyidentified media for filtering fluids flowing from fluid reservoir 664.Filter 688 is preferably constructed from a porous material such apolysulfone.

As indicated in FIG. 54, cover 700 is provided with a tongue 705 andbase 668 is provided with a mating groove 707 which clamp inboardportion 695a of the distendable membrane 695 in position relative to thebase upon cover being brought into pressural engagement with base 668.Similarly, the outboard portion 695b of membrane 695 is clamped againstthe base upon joining the cover to the base by a sonic welding techniqueof the character previously described. Prior to joining the cover andthe base the distendable membrane is bonded to the base along itsperiphery 690a in the manner shown in FIG. 54. When the cover and baseare sealably joined together, conformable ullage 662 is captured betweendistendable membrane 695 and barrier membrane 690. In like fashion,conformable ullage 666 is captured between base portion 670b and theouter periphery of distendable member 695.

In using the apparatus of this latest form of the invention, chambers664 and 666 are first partially filled with a suitable gel via septumassembly 710 (FIG. 60) using a conventional syringe assembly having aneedle "N-1" adapted to penetrate septum 710a of septum assembly 710.During the gel filling step, the gel will flow first into toroidalchamber 666 via passageway 712 and then into central chamber 664 viacircumferentially spaced passageways 694 (FIGS. 53 and 56). This done,fluid reservoir 664a can be filled via septum assembly 586 using asecond syringe assembly containing the beneficial agent to be deliveredto the patient. As the fluid chamber fills, conformable ullage 662 willconform to distendable membrane 695 causing the gel which comprisesullage 662 to be compressed. When chamber 664 reaches capacity, the gelcontained therein can overflow into toroidal chamber 698 via passageways694. With this construction elevated fluid pressures can be accommodatedwithout having to increase the height of chamber 664 and, therefore, theoverall height of the device. During the fluid expelling step, the gelcan, of course, flow in the opposite direction from toroidal chamber 698to central chamber 664 so as to conform to distendable membrane 695 asit tends to return toward its less distended configuration.

With chambers 664 and 698 filled with gel and with fluid reservoir 664afilled with the selected beneficial agent to be delivered to thepatient, the device can be safely stored until time of use. At time ofuse, the novel needle protection means, or protective cover 720 can bebroken away from base 668 along serration 722 (FIG. 57).

As best seen in FIG. 60, protective cover 720 is of unique designcomprising a lower arcuate shaped sheath-like portion 724 which isseparated from a connector portion 726 by serration 722. Sheath portion724, sealably encloses the free floating end 678b of the hollow cannulawhile the upper top open, arcuately shaped segment 726a of the connectorportion 726 is sealably receivable within an opening 727 formed in base668. To hold the protective cover in place, an intermediate, flange-likesegment 726b, which is integrally formed with segment 726a, is bonded tothe lower surface 672 of the base by any suitable means such as adhesivebonding.

Turning to FIGS. 57 and 58, it can be seen that part of the body portion678a and enlarged diameter portion 686 of spiral cannula 678 is uniquelysupported within channel 674 of base 668 by a cannula encapsulationmeans shown here as a standard potting compound 729. Compound 729rigidly supports the body portion of the cannula within channel 674 anddynamically supports the outer extremity 678b of the cannula so that thespring-like outer extremity is free to move three dimensionally withinsegment 726a. With this highly novel construction, when the device isconnected to the patient with the needle portion 678b of the cannulapenetrating the patient's body, as, for example, the patient's arm orleg, normal movement by the patient will permit the cannula to movewithin segment 726a and within the outer portions of channel 674 whilethe base remains completely stationary. Without this important feature,normal movements by the patient causing flexing of the muscle and tissuewould impart loosening forces to the device which, in time, could causethe adhesive pad "A" provided on the base of the device to separate fromthe patient's skin.

Referring to FIGS. 61 through 66, another form of the ultra low profiledevice of the invention is there shown and generally designated by thenumeral 770. As best seen by referring to FIGS. 61, 62, and 63, thisembodiment of the invention is similar in some respects to that shown inFIGS. 43 through 48A save that the filling means is located in adifferent location and the device includes a highly novel hydrogel filmrate control device the character of which will presently be described.

As best seen in FIGS. 61 and 63, the apparatus here comprises a base 772having an upper surface 774, including a central portion 774a and aperipheral portion 774b circumscribing central portion 774a. Base 772 isalso provided with a lower surface 776. Formed within base 772 is aninlet passageway 778 and an outlet passageway 780.

As before, this latest form of the invention includes a stored energymeans for forming, in conjunction with the base 772, a generallytoroidal-shaped fluid reservoir 782 which is in communication withoutlet passageway 780. As best seen in FIG. 63, reservoir 782 is also incommunication with an inlet passageway 778 which, in turn, is incommunication with a septum assembly 786. Filling of reservoir 782 isaccomplished in the manner previously described via septum assembly 786,which is of similar construction to the septum assemblies previouslydescribed herein, and includes a pierceable septum 786a that ispierceable by a syringe needle "N".

Once again, the stored energy means comprises at least one distendablemembrane 796 which is superimposed over base 742. An ullage definingmeans is disposed within a generally toroidal chamber 792 defined by aninner surface 792a formed in a cover 793. Chamber 792 also containsfluid reservoir 782 which is disposed between the inner surface ofmembrane 788 and the upper surface 774 of the base. The ullage definingmeans here comprises a conformable ullage 794 which is interposedbetween membrane 796 and a yieldably deformable barrier membrane 788. Asbefore distendable membrane 796 will distend outwardly upon fluid beingintroduced into reservoir 782 and, after being distended, will tend toreturn to its less distended configuration. Conformable ullage 794 is ofthe same general character as previously described herein and is made upof a deformable mass which uniquely conforms to the shape of thedistendable membrane as the membrane distends and as it tends to returnto its less distended configuration. As encapsulation barrier membrane788 expands, ullage 794 will pressurally engage membrane 796 urging itoutwardly into engagement with surface 792a of cover 793. Distendablemembrane 796, which is elastically deformable, can be constructed fromvarious materials including polyurethane, silicone, flurosilicone andsynthetic rubber.

In the manner previously described, cover 793 is receivable over base772 and, as shown in FIG. 66, includes a capture groove 796 and anadjacent tongue 798. Similarly, base 772 is provided with tongue 800which mates with groove 796 as the cover moves into engagement with base772. As before, base 772 is also provided with an upstanding membranecutting means, or protuberance 802 which functions to cleanly cut thestored energy means and the barrier membrane upon the cover beingbrought into pressural engagement with base. With this construction,following cutting of the membrane, the cover can be sonically welded tothe base.

When the cover and base are sealably joined together, a reservoir inletport 804 communicates with inlet passageway 778, while a reservoiroutlet port 806 communicates with outlet passageway 780. In order toprecisely control the rate of fluid flow outwardly of outlet port 806,rate control means in the form of the previously mentioned hydrogel ratecontrol device 807 is interposed between reservoir 782 and outlet port806. Rate control 807 is constructed from a hydrogel film that swellsupon imbibing fluid entering reservoir 782 and, in its swollencondition, precisely regulates the rate of fluid flow toward outletpassageway 780 and then outwardly of the device through a delivery luerassembly 810 of a character well known in the art. To collect fluidflowing through rate control 807 a fluid collection cavity 812 is formedin base 772 directly below outlet 806.

In using the apparatus of this latest form of the invention, reservoir782 can be filled via septum assembly 786 using a conventional fluidcontaining syringe assembly having a needle "N" adapted to penetrateseptum 786a of septum assembly 786. During filling any gases containedwithin the chamber defined by inner surface 792a of cover 793, will bevented to atmosphere via porous plugs 814 provided in vent apertures 816formed in cover 793 (FIG. 65). With the reservoir thus filled, a cover818, which covers the outlet end of luer assembly 810, can be removedand fluid delivered to the patient in a conventional manner well knownin the art. As before, the base of the device is provided with asuitable adhesive pad 811 to enable the device to be removably affixedto the patient's body such as to the arm or leg of the patient.

Turning next to FIGS. 67 through 71, still another form of the ultra lowprofile infusion device of the invention is there shown and generallydesignated by the numeral 830. This latest embodiment of the inventionis similar in some respects to the embodiment shown in FIGS. 53 through59 in that it also comprises a single fluid reservoir 832 disposedwithin a central chamber 834 formed in a cover 835 and includes aplurality of conformable ullages which are in communication (FIG. 69).More particularly, the device includes a central conformable ullagedefining means, or first conformable mass 836 which is in an inferiorposition to central fluid reservoir 832 and a toroidal-shaped,conformable ullage defining mass, or second conformable mass 838circumscribing ullage 836. This construction permits the use of elevatedpressures within chamber 834 without having to increase the overallheight of the device.

As best seen in FIGS. 67, 68 and 69, the apparatus here comprises a base840 having a first surface 842, including a central portion 842a and aperipheral portion 842b circumscribing central portion 842a. Peripheralportion 842b includes a concave surface 843a which defined a generallytoroidal-shaped expansion channel or groove 843 formed within base 840.Base 840 is also provided with a second surface 844 to which an adhesivepad assembly 846 is affixed. After a peal strip 846a is removed from thepad assembly to expose an adhesive layer "A", the device can beconveniently affixed to the patient's body. Formed within base 840 is acircuitous channel 850 (FIG. 67), which receives a portion of theinfusion means, or serpentine-shaped hollow cannula 852, of theinvention.

The apparatus shown in FIGS. 67 through 71 also includes a uniquelyconfigured stored energy means for forming, in conjunction with thecentral portion 842a of the base, the fluid reservoir 832. Fluidreservoir 832 has an inlet port 856 and an outlet port 860. Inlet port856 is in communication with an outlet port 862a which is provided in anenlarged diameter portion 862 of cannula 852. Filling of fluid reservoir832 is accomplished via a septum assembly 866 of the characterpreviously described having a pierceable septum 866a (FIG. 71). Asbefore, a flow control means comprises the micro bore portion 852a ofthe cannula.

The stored energy means is here provided in the form of a generallyplanar distendable membrane 870 which overlays surface 842 of the base.Membrane 870 includes an inner O-ring like protuberance or portion 870aand a radially spaced, outer O-ring like protuberance portion 870b.These O-ring like protuberances form a part of the sealing means of theinvention for sealably interconnecting base 840 and cover 835 and aresealably received within generally circular-shaped, radially spacedinner and outer O-ring grooves 872a and 872b formed in surface 842 ofbase 840 (see FIGS. 67 and 68). Grooves 872a and 872b also form a partof the sealing means of the invention. When the apparatus is assembledin the manner shown in FIG. 69, membrane 870 spans central portion 842aas well as the circumferentially extending grooved outer portion 842b ofbase 840. The inner and outer O-ring like protuberances are alsosealably receivable within O-ring grooves 873a and 873b which are formedin cover 835 and which also comprise a part of the sealing means of theinvention. Materials suitable for use in constructing the base, thecover and the distendable membrane are discussed in detail in U.S. Pat.No. 5,205,820 (FIG. 68).

Disposed within a generally circular shaped recess 875 formed in base840 is a barrier means or separation membrane 877 which prevents fluidwithin fluid chamber 832 from contacting distendable membrane 870.Membrane 877 can be formed from any suitable elastomeric material suchas polyurethane, silicone or synthetic rubber.

With the construction shown in FIG. 69, the central or first conformablemass 836 of the ullage defining means is disposed within chamber 834 forengagement with membrane 870 which, after being distended, will tend toreturn to its less distended configuration. As was the case with thepreviously discussed embodiment shown in FIGS. 53 through 59), theullage defining means of this latest embodiment of the inventioncomprises not only the central conformable ullage 836, but also theouter toroidal shaped, conformable ullage 838. Both of the conformablemasses 836 and 838 are uniquely covered by distendable membrane 870 andboth continuously vary in shape as the distendable membrane distendsoutwardly from the base (FIG. 69).

A unique feature of this latest embodiment of the invention results inthe fact that the first conformable mass ullage 836 communicates withthe second outer toroidal-shaped mass 838 via a plurality of passageways878 which interconnect the first or central chamber 834 formed in cover835 with the second toroidal-shaped chamber 792 formed in cover 835(FIG. 69). As before, conformable masses 836 and 838 preferably comprisea deformable, flowable mass constructed from a suitable gel material.Accordingly, in a manner presently to be described, the gel which makesup first conformable mass 836 can expand into chamber 792 formed incover 835 via passageways 878 as the distendable membrane 870 distendsoutwardly during filling of fluid chamber 832.

Turning particularly to FIGS. 67, 68 and 69, the serpentine-shapedcannula 852 of the device includes the previously identified enlargeddiameter portion 862 and the microbore portion 852a which terminates ina needle-like outboard extremity 852b. As best seen in FIG. 70, theenlarged diameter portion 862 of the cannula is held in position withinchannel 850 by a potting compound 422 of the character previouslydescribed.

Turning particularly to FIG. 68, it can be seen that cover 835 isprovided with an upstanding protuberance 883 which permits joining ofthe cover 835 to the base 840 by a sonic welding technique of thecharacter previously described. Prior to joining the cover and the baseand, prior to positioning the distendable membrane over the cover,chambers 834 and 792 are filled with gel. Also, barrier membrane 877 is,at this time, appropriately bonded to the base along its periphery byadhesive bonding or like techniques well known to those skilled in theart. When the cover and base are sealably joined together, the O-ringprotuberances 870a and 870b are guided into sealable engagement withgrooves 872a and 872b respectively so as to seal distendable membrane870 relative to the base. If desired, a suitable adhesive can be placedwithin grooves 872a and 872b to bond the O-ring-like portions 870a and870b to the base to enhance sealing. After the cover and base have beeninterconnected, conformable ullages 836 and 838 are sealably capturedbetween distendable membrane 870 and the inner surfaces of cover 835which define chambers 834 and 792.

Following the interconnection of base 840 with cover 835 in the mannerdescribed in the preceding paragraphs, fluid reservoir 832 can be filledvia septum assembly 866 using a suitable syringe assembly containing thebeneficial agent to be delivered to the patient. As the fluid chamberfills, conformable mass 836 will conform to the central portion of thedistendable membrane in the manner shown in FIG. 69 causing the gelwhich comprises mass 836 to be forced inwardly and to overflow into thesecond toroidal-shaped chamber 792 via passageways 878. As the gel flowsunder pressure into chamber 792, the outer peripheral portion 870c ofdistendable membrane 870 will deform toward concave surface 843a andinto base channel 843 permitting this channel to, at least, partiallyfill with gel. As the peripheral portion 870c of the distendablemembrane 870 distends into channel 843, any gases contained therein willbe vented to atmosphere via vent means which here comprises a passageway840d and a vent plug 879 (see FIG. 69). With this novel construction,elevated fluid pressures within the fluid chamber 834 can readily beaccommodated without having to increase the height of the chamber and,therefore, the overall height of the device. During the fluid expellingstep, the gel can, of course, flow in the opposite direction fromtoroidal-shaped chamber 792 into first or central chamber 834 so as toconform to distendable membrane 870 as it tends to return toward itsless distended configuration.

With chambers 834 and 792 filled with gel and with fluid reservoir 832filled with the selected beneficial agent to be delivered to thepatient, the device can be safely stored until time of use. At time ofuse, the novel needle protection means, or protective cover 885 can bebroken away from base 840 along serration 887 (FIG. 69) and removed fromthe cannula thereby permitting fluid to flow outwardly of cannula end852b.

Referring now to FIGS. 72, 73, and 74, another form of the ultra lowprofile infusion device of the invention is there shown and generallydesignated by the numeral 900. This latest embodiment of the inventionis similar in many respects to the embodiment shown in FIGS. 67 through71 and like numbers are used to identify like components. This latestembodiment of the invention comprises a single fluid reservoir 902 (FIG.74) disposed within a first central chamber 834 formed in a cover 835which is identical to that previously described and includes conformablemasses 836 and 838 of the character previously described which are incommunication via passageways 878.

As best seen in FIGS. 73 and 74, base 906 of this embodiment is of aslightly different construction having a central, generally convexsurface 906a and a peripheral portion 906b which includes a concavesurface 910a which defines a generally toroidal-shaped expansion channelor groove 910 formed within base 906. In this latest form of theinvention, convex portion 906a, in cooperation with the conformablemasses 836 and 838, comprise the ullage means of the invention. Asbefore, base 906 has a surface 906c to which an adhesive pad assembly912 is affixed. Integrally molded within base 906 is a serpentine-shapedhollow cannula 914, which comprises a part of the infusion means of thisform of the invention.

The apparatus shown in FIGS. 72 through 74 includes a uniquelyconfigured stored energy means identical to that described in connectionwith the embodiment shown in FIGS. 67 through 71 and forms, inconjunction with the central portion 906a of the base, the fluidreservoir 902. Fluid reservoir 902 has an inlet port 916 and an outletport 920. Inlet port 916 is in communication with an outlet port 914awhich is provided in an enlarged diameter portion 914b of cannula 914.Filling of fluid reservoir 902 is accomplished via a septum assembly 866of the character previously described having a septum 866a.

In this latest form of the invention, flow control means comprises botha uniquely shaped hydrogel rate control device 918 as well as the microbore portion 914c of the cannula. Rate control device 918 is held inplace within a recess 921 formed in base 906 by any suitable means suchas adhesive bonding. In use, the hydrogel rate control device swellsupon imbibing fluid and functions to precisely control the rate of fluidflow from reservoir 902.

As in the earlier described form of the invention, the stored energymeans or membrane 870, overlays the base and includes an inner O-ringlike protuberance 870a and a radially spaced, outer O-ring likeprotuberance 870b. These O-ring like protuberances are sealably receivedwithin generally circular-shaped, radially spaced inner and outer O-ringgrooves 872a and 872b formed in base 906 (see FIGS. 73 and 74). Asbefore, grooves 872a and 872b also form a part of the sealing means ofthe invention. When the apparatus is assembled in the manner shown inFIG. 74, membrane 870 spans the central portion of the base as well asthe circumferentially extending grooved outer portion 906b. The innerand outer O-ring like protuberances are also sealably receivable withinO-ring grooves 873a and 873b formed in cover 835 (FIG. 73) and whichcomprise a part of the sealing means of the invention.

In the construction shown in FIG. 74, the central convex portion 906a ofthe base forms the rigid ullage portion of the ullage means and ullageportions 836 and 838 form the conformable ullage portions of the ullagemeans. As before, the conformable ullage portions of the ullage meansare covered by distendable membrane 870 and both continuously vary inshape as the distendable membrane distends outwardly from the base asfluid is introduced into reservoir 902 via the septum assembly. Onceagain, central conformable ullage 836 communicates with the outertoroidal ullage 838 via passageways 878 so that, as fluid chamber 902 isfilled, the gel which makes up the central ullage is engaged by membrane870 urging it outward and causing it to flow into chamber 792 of cover835. This causes the gel contained within this chamber to, in turn,expand, along the membrane 870 into channel 910 formed in base 906 inthe manner shown in FIG. 74.

Turning particularly to FIGS. 72, 72A, and 73, the serpentine-shapedcannula 914 of the device there illustrated includes the previouslyidentified enlarged diameter portion 914b and the microbore portion 914cwhich terminates in a needle-like outboard extremity 914d. Cannula 914is molded in place with a base 906 in a manner well known by thoseskilled in the art. Extremity 914d is protected by a protective cover885a which is similar to the previously discussed cover 885. However,cover 885a includes an outer sheath 885b which is connected to the basealong a serration line 887. Sheath 885b telescopically receives aremovable plug 887c which closely surrounds extremity 914d of thecannula.

Prior to joining the cover and the base as by sonic welding and, priorto positioning the distendable membrane over the cover, chambers 834 and792 are filled with gel. Also, rate control device 918 is, at this time,emplaced into cavity 921. When the cover and base are sealably joinedtogether, the O-ring portions 870a and 870b are guided into sealableengagement with grooves 873a and 873b respectively so as to sealdistendable membrane 870 relative to the base. If desired, a suitableadhesive can be placed within grooves 872a and 872b to bond theO-ring-like portions 870a and 870b to the base to enhance sealing. Afterthe cover and base have been interconnected, conformable ullages 836 and838 are sealably captured between distendable membrane 870 and the innersurfaces of cover 835 which define chambers 834 and 792.

Following the interconnection of base 906 with cover 835 in the mannerdescribed in the preceding paragraphs, fluid reservoir 902 can be filledvia septum assembly 866 using a suitable syringe assembly containing thebeneficial agent to be delivered to the patient. Filter means, shownhere as a porous filter member 923, filters the fluid flowing out ofoutlet 914a. Filter 923 can be constructed from any suitable filtermaterial such as a polycarbonate. As the fluid chamber fills, theperipheral portion 870c of the distendable membrane 870 will distendinto channel 910, and any gases contained therein will be vented toatmosphere via passageway 925 and vent plug 927 (see FIG. 74). Duringthe fluid expelling step, the gel can, of course, flow in the oppositedirection from toroidal chamber 792 into central chamber 834 so as toconform to distendable membrane 870 as it tends to return toward itsless distended configuration.

Turning next to FIGS. 75 through 79, still another form of the ultra lowprofile infusion device of the invention is there shown and generallydesignated by the numeral 950. This latest embodiment of the inventionis somewhat similar to the embodiment shown in FIGS. 72 through 74 andlike numbers are used to identify like components. This latestembodiment of the invention uniquely comprises a dual chamber fluidreservoir 952 (FIG. 76) which extends into a central chamber 954 formedin a cover 956 which is similar to that previously described. However,central chamber 954 is slightly larger to accommodate the dual chamberfluid reservoir. As before, cover 956 contains a plurality ofconformable masses of the character previously described which are incommunication via passageways 957.

As best seen in FIGS. 75 and 76, base 960 of this embodiment is of aslightly different construction having first and second filling meansfor separately filling the dual reservoirs 952a, and 952b. Like theearlier described embodiment, base 960 has a central, surface 960a and aperipheral portion 960b which includes a generally toroidal-shapedexpansion channel or groove 962 formed within base 960 and defined byconcave surface 962a. In this latest form of the invention, portion 960ais generally planar in shape. Base 960 also has a surface 960c to whichan adhesive pad assembly 964 is affixed. Integrally molded within base960 is a uniquely-shaped hollow cannula 966 (FIG. 79), which comprises apart of the infusion means of this form of the invention.

The apparatus shown in FIGS. 75 through 77 includes a uniquelyconfigured stored energy means very similar to that previously describedand, in conjunction with the central portion 960a of the base, forms thetwo fluid reservoirs 952a and 952b. As best seen in FIGS. 75, 76, and77, fluid reservoir 952a has an inlet port 968 and an outlet port 970.Similarly, fluid reservoir 952b has an inlet port 972 and an outlet port974. Outlet ports 970 and 974 communicate with inlet ports 975 and 977respectively provided in enlarged diameter portion 966a of cannula 966(FIG. 79). Filling of reservoir 952a is accomplished via a first septumassembly 980 of the character previously described, while fluidreservoir 952b is filled via septum assembly 982. As best seen in FIG.78, each of the septum assemblies communicate with an elongated tubularmember "T" which terminates at its reduced diameter end at the inlets offluid reservoirs 952a and 952b.

In this latest form of the invention, flow control means are provided inthe form of first and second rate control members 983 and 984respectively which are disposed within cavities 983a and 984a formed inbase 960 proximate outlets 970 and 974. Members 983 and 984 arepreferably constructed from a polycarbonate material.

As in the earlier described form of the invention, the stored energymeans or membrane 986, overlays the base and includes an inner O-ringlike protuberance 986a and a radially spaced, outer O-ring likeprotuberance 986b. These O-ring like protuberances are sealably receivedwithin generally circular-shaped, radially spaced inner and outer O-ringgrooves 987a and 987b formed in base 960 (see FIG. 75A). When theapparatus is assembled in the manner shown in FIG. 76, membrane 986spans the central portion of the base as well as the circumferentiallyextending grooved outer portions 960b. The inner and outer O-ring likeprotuberances are also sealably receivable within O-ring grooves 989aand 989b formed in cover 956 (FIG. 75A).

Provided in the construction shown in FIGS. 75 and 77, is a highly novelbarrier or separation means, shown here as a yieldable separationmembrane 990. As best seen in FIG. 75, membrane 990 is bonded to thebase along the peripheral portions "P" thereof and along a centraldividing line "L" that divides the membrane into first and secondportions 990a and 990b. More particularly, the membrane is bonded to thebase along the bond areas designated generally as 991. Areas 991acircumscribe central portion 960a while area 991b bisects the centralportion. With this novel construction, as fluid under pressure isintroduced into the device via the first and second filling means, boththe stored energy membrane 986 and the barrier membrane 990 will deformoutwardly in the manner shown in FIG. 76 to form the two fluidreservoirs.

As before, the ullage means are covered by distendable membrane 986 andboth continuously vary in shape as the distendable membrane distendsoutwardly from the base as fluid is introduced into reservoirs 952a and952b via septum assemblies 980 and 982. Once again, the centralconformable ullage or mass 994 communicates with the outer toroidalullage or mass 995 via passageways 957 so that, as fluid chambers 952aand 952b are filled, the mass which makes up the central ullagecontained within central chamber 954 is engaged by membrane 986 urgingit outward and causing it to flow into toroidal chamber 956b of cover956. This causes the mass contained within this chamber along withmembrane 986 to, in turn, expand into channel 962 formed in base 960 inthe manner shown in FIG. 76. As before, gases contained in this channelwill be vented via passageway 925 and vent plug 927. As the fluid isexpelled from the reservoirs, the gel-like masses will return to thecentral chamber in the manner shown in FIG. 77A.

Turning particularly to FIGS. 77 and 79, the uniquely-shaped cannula 966of the device there illustrated includes the previously identifiedenlarged diameter portion 966a and the smaller diameter portion 966bwhich terminates in a needle-like outboard extremity 966c. Cannula 966is molded in place with a base 960 in a manner well known by thoseskilled in the art.

Prior to joining the cover and the base as by adhesive bonding or sonicwelding and, prior to positioning the distendable membrane over thecover, chambers 954 and 956b are filled with the gel which comprises theconformable masses 994 and 995. Also, rate control membranes 983 and 984are, at this time, emplaced into cavities 983a and 984a and barriermembrane 990 is adhesively bonded to base 960 along bond areas 991a and991b. When the cover and base are sealably joined together, the O-ringprotuberances 986a and 986b are guided into sealable engagement withgrooves 987a and 987b respectively so as to seal distendable membrane986 relative to the base. If desired, a suitable adhesive can be placedwithin the grooves to bond the O-ring-like protuberances to the base andto the cover to enhance sealing. After the cover and base have beeninterconnected, conformable ullages 994 and 995 are sealably capturedbetween distendable membrane 986 and the inner surfaces of cover 956which define chambers 954 and 956b.

Following the interconnection of base 960 with cover 956 in the mannerdescribed in the preceding paragraphs, fluid reservoir 952a can befilled via septum assembly 980 using a suitable syringe assemblycontaining the beneficial agent to be delivered to the patient. As thefluid is introduced via septum assembly 980 and tube "T", it willimpinge upon portion 990a of membrane 990 causing it, along with aportion of distendable membrane 986, to distend outwardly to formreservoir 952a. In similar fashion, fluid reservoir 952b can be filledvia septum assembly 982. Once again, as fluid is introduced into thedevice via septum assembly 982, and tube "T" it will impinge uponportion 990b of membrane 990 causing it, along with a portion ofdistendable membrane 986, to distend outwardly to form reservoir 952b.As the central portions of the distendable membrane 986 thusly extendsoutwardly, the peripheral portion thereof will extend into channel 962in the manner shown in FIG. 76. Fluid flowing into reservoirs 952a and952b will be filtered by filter means shown here as porous filter "F"which are carried within tubes "T".

As fluid is expelled from reservoirs 952a and 952b in the manner shownin FIG. 77A, the central portion of the distendable membrane will movetoward the central portion of the base causing fluid to flow into inletports 975 and 977 of the cannula via rate controls 983 and 984. At thesame time, the peripheral portion of the distendable membrane will causeconformable mass 995 to flow toward central chamber 954 in the mannershown in FIG. 77a.

Turning next to FIGS. 80 through 87, another form of the ultra lowprofile infusion device of the present invention is there shown andgenerally designated by the numeral 1000. This latest embodiment of theinvention is similar in some respects to the embodiment shown in FIGS.67 through 71, but comprises a sealing means of different constructionfor sealably interconnecting the distendable membrane with the base andwith the cover. This latest form of the invention also comprises asingle fluid reservoir 1002 disposed within a central chamber 1004formed in a cover 1005 and includes a plurality of conformable ullageswhich are in communication (FIG. 86). More particularly, the deviceincludes a central conformable ullage defining means, or firstconformable mass 1006 which is in an inferior position to central fluidreservoir 1002 and a toroidal-shaped, conformable ullage defining mass,or second conformable mass 1008 circumscribing ullage 1006.

As best seen in FIGS. 83 and 86, the apparatus here comprises a base1010 having a first surface 1012, including a central portion 1012a anda peripheral portion 1012b circumscribing central portion 1012a.Peripheral portion 1012b includes a concave surface 1013a which defineda generally toroidal-shaped expansion channel or groove 1013 formedwithin base 1010. As before, base 1010 is also provided with a secondsurface 1014 to which an adhesive pad assembly 1016 is affixed. After apeal strip is removed from the pad assembly to expose a thin adhesivelayer "A", the device can be conveniently affixed to the patient's body.Formed within base 1010 is a bore 1020 (FIG. 83), which receives aportion of the infusion means, or hollow cannula 1022, of the invention.

The apparatus shown in FIGS. 80 through 87 also includes a stored energymeans for forming, in conjunction with the central portion of the base,the fluid reservoir 1002. Fluid reservoir 1002 has an inlet port 1026and an outlet port 1030. Inlet port 1026 is in communication with anoutlet port 1032a which is provided in an enlarged diameter portion1022a of cannula 1022. Filling of fluid reservoir 1002 is accomplishedvia a septum assembly 1036 of the character previously described havinga pierceable septum 1036a (FIG. 84). As before, a flow control meanscomprises the micro bore portion 1022b of the cannula. The flow controlmeans in this latest embodiment of the invention also comprises a flowcontrol member 1038, the character of which will presently be described.

The stored energy means is here provided in the form of a generallyplanar distendable membrane 1040 which overlays surface 1012 of thebase. When the apparatus is assembled in the manner shown in FIG. 86,membrane 1040 spans central portion 1012a as well as thecircumferentially extending channeled outer portion 1012b of base 1010.Membrane 1040 is sealably receivable within ring-like grooves 1043 and1045 which are formed in cover 1005 (FIG. 83). Grooves 1043 and 1045form a part of the sealing means of this embodiment of the invention asdo inner and outer ring-like protuberances 1047 and 1049 formed on base1010. As best seen by referring to FIG. 86, when base 1010 and cover1005 are joined together, protuberance 1047 is closely received withingroove 1043 and protuberance 1049 is closely received within groove 1045in a manner to sealably clamp inner and outer ring-like portions 1040aand 1040b of distendable membrane 1040 between base 1010 and cover 1005.

Disposed within a generally circular shaped recess 1054 formed in base1010 is a barrier means or separation membrane 1056 which prevents fluidwithin fluid reservoir 1002 from contacting distendable membrane 1040.Membrane 1056 can be formed from any suitable elastomeric material suchas polyurethane, silicon or synthetic rubber.

With the construction shown in FIG. 86, the central or first conformablemass 1006 of the ullage defining means is disposed within chamber 1004for engagement with membrane 1040 which, after being distended, willtend to return to its less distended configuration. As was the case withthe previously discussed embodiment, the ullage defining means of thislatest embodiment of the invention comprises not only the centralconformable ullage 1006, but also the outer toroidal shaped, conformableullage 1008. Both of the conformable masses 1006 and 1008 are uniquelycovered by distendable membrane 1040 and both continuously vary in shapeas the distendable membrane distends outwardly from the base (FIG. 86).

As before in this latest embodiment of the invention first conformablemass ullage 1006 communicates with the second outer toroidal-shaped mass1008 via passageways 1061 which interconnect the first or centralchamber 1004 formed in cover 1005 with the second toroidal-shapedchamber 1064 formed in cover 1005 (FIG. 83). As before, conformablemasses 1006 and 1008 preferably comprise a deformable, flowable massconstructed from a suitable gel material. Accordingly, in a mannerpresently to be described, the gel which makes up first conformable mass1006 can expand into chamber 1064 formed in cover 1005 via passageways1061 as the distendable membrane 1040 distends outwardly during fillingof fluid chamber 1002.

Turning particularly to FIGS. 81, 83 and 86, the generally straightcannula 1022 of the device includes the previously identified enlargeddiameter portion 1022a and the microbore portion 1022b which terminatesin an outboard extremity 1022c which is suitably interconnected with aluer connector 1065. In this latest form of the invention, the cannulais molded in place within bore 1020.

Turning particularly to FIG. 83, it can be seen that, as before, cover1005 is provided with an upstanding protuberance 1067 which permitsjoining of the cover 1005 to the base 1010 by a sonic welding techniqueof the character previously described. Prior to joining the cover andthe base and, prior to positioning the distendable membrane over thecover, chambers 1004 and 1064 are filled with gel. Also barrier membrane1056 is, at this time, appropriately bonded to the base by adhesivebonding or like techniques well known to those skilled in the art. Whenthe cover and base are sealably joined together, the ring-likeprotuberances 1047 and 1049 are guided into grooves 1043 and 1045respectively so as to sealably clamp distendable membrane 1040 securelybetween the base and the cover. If desired, a suitable adhesive can beplaced within grooves 1043 and 1045 to bond portions 1040a and 1040b ofthe distendable membrane to the cover to enhance sealing. After thecover and base have been interconnected, conformable ullages 1006 and1008 are sealably captured between distendable membrane 1040 and theinner surfaces of cover 1005 which define chambers 1004 and 1064. It isto be noted that chambers 1004 and 1064 can also be filled with gel viaa fill port 1005f and a passageway 1005p (FIG. 86)

Following the interconnection of base 1010 with cover 1005 in the mannerdescribed in the preceding paragraphs, fluid reservoir 1002 can befilled via septum assembly 1036 using a suitable syringe assemblycontaining the beneficial agent to be delivered to the patient. As thefluid chamber fills, conformable mass 1006 will conform to the centralportion of the distendable membrane in the manner shown in FIG. 86causing the gel which comprises mass 1006 to be forced inwardly and tooverflow into the second toroidal-shaped chamber 1064 via passageways1061. As the gel flows under pressure into chamber 1064, the outerperipheral portion of the distendable membrane 1040 will deform towardconcave surface 1013a and into base channel 1013 permitting this channelto, at least, partially fill with gel. As the peripheral portion of thedistendable membrane distends into channel 1013, any gases containedtherein will be vented to atmosphere via vent means which here comprisesa passageway 1069 and a vent plug 1071 (see FIGS. 80 and 82).

During the fluid expelling step, the gel can, of course, flow in theopposite direction from toroidal-shaped chamber 1064 into first orcentral chamber 1004 so as to conform to distendable membrane 1040 as ittends to return toward its less distended configuration.

With chambers 1004 and 1064 filled with gel, with fluid reservoir 1002filled with the selected beneficial agent to be delivered to the patientand with the luer connector 1065 connected to a valved administrationline, the device can be safely stored until time of use. At time of use,the administration line can be opened to fluid flow toward the patient.

Turning to FIG. 85 a slightly different form of cannula and septum isthere illustrated. Here the fill end of cannula 1023 is bell shaped tosealably receive a matching shaped septum 1037a. This alternate designis better suited for certain end applications of the device.

Referring now to FIGS. 88 through 94, still another form of the ultralow profile infusion device of the invention is there shown andgenerally designated by the numeral 1100. This latest embodiment of theinvention is similar in many respects to the embodiment shown in FIGS.80 through 87 and like numbers are used to identify like components.This latest embodiment of the invention comprises a single fluidreservoir 1102 (FIG. 93) disposed within a first central chamber 1004formed in a cover 1005 which is identical to that previously describedin connection with the embodiment of FIGS. 80 through 87 and includesconformable masses 1006 and 1008 of the character previously describedwhich are in communication via passageways 1061.

As best seen in FIGS. 91 and 93, base 1106 of this embodiment is of aslightly different construction having a central, generally convexsurface 1106a and a peripheral portion 1106b which includes a concavesurface which defines a generally toroidal-shaped expansion channel orgroove 1110 formed within base 1106. In this latest form of theinvention, convex portion 1106a, in cooperation with the conformablemasses 1006 and 1008, comprise the ullage means of the invention. Asbefore, base 1106 has a surface 1106c to which an adhesive pad assembly1016 is affixed. Integrally molded within base 1106 is a hollow cannula1114, which comprises a part of the infusion means of this form of theinvention.

The apparatus shown in FIGS. 88 through 94 includes a uniquelyconfigured stored energy means identical to that described in connectionwith the embodiment shown in FIGS. 80 through 87 and forms, inconjunction with the central portion 1106a of the base, the fluidreservoir 1102. Fluid reservoir 1102 has an inlet port 1116 and anoutlet port 1120. Inlet port 1116 is in communication with an outletport 1114a which is provided in an enlarged diameter portion 1114b ofcannula 1114. Filling of fluid reservoir 1102 is accomplished via aseptum assembly 1036 of the character previously described having aseptum 1036a.

In this latest form of the invention, flow control means comprises botha uniquely shaped hydrogel rate control device 1118 as well as the microbore portion 1114c of the cannula. Rate control device 1118 is held inplace within a recess 1121 formed in base 1106 by any suitable meanssuch as adhesive bonding. In use, the hydrogel rate control deviceswells upon imbibing fluid and functions to precisely control the rateof fluid flow from reservoir 1102.

As in the earlier described form of the invention, the stored energymeans or membrane 1040, overlays the base and is sealably interconnectedwith cover 1005 in the same manner as described in connection with theform of the invention shown in FIGS. 80 through 87. When the apparatusis assembled in the manner shown in FIG. 93, membrane 1040 spans thecentral portion of the base as well as the circumferentially extendingchanneled outer portion 1106b. Inner and outer ring-like protuberances1123 and 1125 are sealably receivable within ring-like grooves 1043 and1045 which are formed in cover 1005 (FIG. 91) and which comprise a partof the sealing means of the invention.

In the construction shown in FIG. 94, the central convex portion 1106aof the base forms the rigid ullage portion of the ullage means andullage portions 1006 and 1008 form the conformable ullage portions ofthe ullage means. As before, the conformable ullage portions of theullage means are covered by distendable membrane 1040 and bothcontinuously vary in shape as the distendable membrane distendsoutwardly from the base as fluid is introduced into reservoir 1102 viathe septum assembly. Once again, central conformable ullage 1006communicates with the outer toroidal ullage 1008 via passageways 1061 sothat, as fluid chamber 1102 is filled, the gel which makes up thecentral ullage is engaged by a barrier membrane 1128 which is disposedbetween distendable membrane 1040 and cover 1005. With thisconstruction, as reservoir 1102 fills membranes 1040, 1127, and 1128will distend outwardly in the manner shown in FIG. 93 causing gel 1006to flow into chamber 1064 of cover 1005. This causes the gel containedwithin this chamber to, in turn, expand, along with the membrane 1040into channel 1110 formed in base 1106 in the manner shown in FIG. 93.

As before, in FIG. 89, cannula 1114 includes the previously identifiedenlarged diameter portion 1114b and the microbore portion 1114c whichterminates in an extremity 1114d which communicates with a noveldelivery luer assembly 1131, the character of which will presently bedescribed.

Prior to joining the cover and the base as by sonic welding and, priorto positioning the distendable membrane 1040 and the containment film1128 over the cover, chambers 1004 and 1064 are filled with theconformable mass or gel. Containment film 1128 can be constructed fromvarious materials such as cellulose acetate, polyethylene, polypropylenepolyvinyl films and the like and functions to contain the mass or gelwithin the cover. Also, rate control device 1118 is, at this time,emplaced into cavity 1121 and a first barrier membrane 1127 is affixedalong its periphery to the central portion of base 1106. When the coverand base are sealably joined together, the ring-like protuberances 1123and 1125 formed on base 1106 are guided into sealable engagement withgrooves 1043 and 1045 respectively so as to sealably clamp bothdistendable membrane 1040 and film 1128 between the base and the cover.If desired, a suitable adhesive can be placed within grooves 1043 and1045 to bond to the two membranes and to the cover to enhance sealing.After the cover and base have been thusly interconnected, conformableullages 1006 and 1008 are sealably captured between containment film1128 and the inner surfaces of cover 1005 which define chambers 1004 and1064.

Following the interconnection of base 1106 with cover 1005 in the mannerdescribed in the preceding paragraphs, fluid reservoir 1102 can befilled via septum assembly 1036 using a suitable syringe assemblycontaining the beneficial agent to be delivered to the patient. Filtermeans, shown here as a porous filter member 1135, filters the fluidflowing out of outlet 1114a. Filter 1135 can be constructed from anysuitable filter material such as a polycarbonate and is backed by afluid blocking means shown here as a blocking membrane 1135a. Blockingmembrane 1135a functions to direct the fluid flowing into cannulaportion 1114b toward fluid reservoir 1102. As the fluid chamber fills,the peripheral portions of the distendable membrane 1040 and the barriermembrane 1128 will distend into channel 1110, and any gases containedtherein will be vented to atmosphere via passageway 1006a and vent plug1071 (see FIG. 88). During the fluid expelling step, the gel can, ofcourse, flow in the opposite direction from toroidal chamber 1064 intocentral chamber 1004 so as to conform to barrier membrane 1128 as ittends, along with the distendable membrane, to return toward their lessdistended configuration.

Turning particularly to FIG. 92 the novel dispensing means of the formof the invention is there illustrated. This dispensing means includesthe previously identified quick connect delivery fitting 1131 having atapered inboard end 1131a which is telescopically and sealablyreceivable within a tapered bore 1142 formed in base 1106 (FIG. 91). Inorder to releasably lock fitting 1131 in position within bore 1142 andin fluid communication with end 1114d of cannula 1114, locking meansshown here as resiliently deformable locking tabs 1144 are provided onbase 1106. Extending from the end of quick connect fitting assembly 1131is an infusion set 1146 having a soft cannula assembly 1150, theoperation of which is well understood by those skilled in the art. Oncethe soft cannula 1150a has been introduced into the patients subdermaltissues "ST" in the manner shown in FIG. 92, the cannula insertionassembly 1152, which includes a trocar 1152a, can be removed leaving thesoft cannula 1150a in position within the patient. Needle cannulainterconnect 1154a of the connector assembly 1154 of the infusion set1146 can then be inserted into assembly 1150 and interconnectedtherewith using the latch mechanism 1155. Connector assembly 1154 whichforms a part of infusion set 1146, when connected with assembly 1150,places soft cannula 1150a in a fluid communication with reservoir 1102.Infusion set 1146 is of a character well known in the art and is readilyavailable from several commercial sources including Pharma-PlastInternational A/S of Lynge, Denmark. By pushing inwardly on locking tabs1144, delivery quick connect 1131 can be urged into bore 1142 to aposition wherein locking tabs 1144 will close about member 1131 and inengagement with a shoulder 1131b formed on member 1131 so as to securelylock the dispensing means to the base.

In each of the embodiments of the invention described in the foregoingparagraphs which include ullage defining means, this means can beconstructed not only from the previously described materials, but alsofrom oils, such as mineral oil, corn oil, peanut oil, silicon oil, andcottonseed oil. Additionally, the ullage defining means can beconstructed from materials such as sodium palmitate and sodium stearate,water, glycerine, air and methyl cellulose.

Similarly, in each of the embodiments of the invention as previouslydescribed which include barrier membranes, the barrier membranes can beformed from materials such as polyurethane, fluorosilicone,polypropylene, polyethylene and copolymers of these materials. Amaterial particularly well suited for use in constructing the barriermembrane is a copolymer of polyethylene and polypropylene sold by ShellOil Company under the name and style "Krayton".

Having now described the invention in detail in accordance with therequirements of the patent statutes, those skilled in this art will haveno difficulty in making changes and modifications in the individualparts or their relative assembly in order to meet specific requirementsor conditions. Such changes and modifications may be made withoutdeparting from the scope and spirit of the invention, as set forth inthe following claims.

We claim:
 1. A device for use in infusing medicinal fluid into a patientat a controlled rate comprising:(a) a base having an upper surfaceincluding a central portion and a peripheral portion circumscribing saidcentral portion, a lower surface and a channel formed in said base, saidchannel having non-linear shaped portions and first and second ends; (b)stored energy means for forming in conjunction with said base, agenerally toroidal-shaped reservoir having an outlet, said stored energymeans comprising at least one distendable membrane superimposed oversaid base, said membrane being distendable as a result of pressureimparted by fluids introduced into said reservoir to establish internalstresses, said stresses tending to move said membrane toward a lessdistended configuration; (c) ullage defining means disposed within saidreservoir for engagement by said distendable membrane, said ullagedefining means comprising a yieldable mass that is substantiallyconformable to the shape of said distendable membrane as said membranetends to move toward a less distended configuration; and (d) infusionmeans for infusing medicinal fluid from said fluid reservoir into thepatient, said infusion means having an inlet end disposed proximate saidchannel and including a hollow cannula having:(i) a central body portiondisposed within said channel; and (ii) an outlet end portion including aportion extending substantially perpendicularly outward substantiallyfrom said lower surface of said base for insertion into the patient. 2.A device as defined in claim 1 further including fluid flow controlmeans disposed between said reservoir and said inlet end of saidinfusion means.
 3. A device as defined in claim 1 further including acover affixed to said base, said cover having a concave surface formedtherein for receiving said ullage means.
 4. A device as defined in claim1 further including fluid inlet means for introducing fluid into saidfluid reservoir, said fluid inlet means comprising a pierceable septummounted in said base.
 5. A device as defined in claim 4 in which saidhollow cannula includes an inlet portion for receiving a portion of saidpierceable septum.
 6. A device as defined in claim 4 further including aprotective sheath removably connected to said base for surrounding andprotecting said pierceable portion of said hollow cannula.
 7. A deviceas defined in claim 6 further including a cannula closure telescopicallyreceivable within said protective sheath, said closure having a centralbore for receiving said pierceable portion of said hollow cannula.